Apparatus and method for continuous non-invasive cardiovascular monitoring

ABSTRACT

Apparatus and related methods for continuous long-term non-invasive measurement of the pressure of a pulsatile fluid flowing through a flexible tube, particularly human arterial blood flow, is disclosed. Specifically, the apparatus provides a continuous calibrated pressure measurement by first undertaking a &#34;calibration&#34; phase comprised of determining the pressure at various pre-defined conditions of flow and, in reponse thereto, ascertaining the values of a plurality of coefficients each of which is associated with a corresponding term in a pre-defined function that characterizes fluid pressure in relation to pulsatile displacement of the wall of the tube; and second, undertaking a &#34;continuous monitoring&#34; phase comprised of determining each subsequently occurring pressure value as the pre-defined function of each corresponding pulsatile wall displacement value, and re-initiating the calibration phase at the expiration of pre-defined time intervals which adaptively change based upon current and prior results. Methods, which are particularly useful in conjunction with the disclosed apparatus, for ascertaining systolic and diastolic arterial blood pressure values are also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to an apparatus and various methods used thereinfor continuous non-invasive measurement of the pressure of a pulsatilefluid flowing through a flexible tube over relatively long time periods,with particular applicability to the measurement of human arterial bloodpressure and other related cardiovascular parameters.

2. Description of the Prior Art

Often a need arises to monitor pulsatile fluid pressure in a vesselwhere a number of practical considerations preclude direct invasivemeasurement, i.e. using an appropriate pressure sensor directlyimplanted through the vessel and maintained in a suitable positionwithin the fluidic flow. Considerations of this nature include avoiding:contamination of the fluid or its immediate environment by any foreignmatter carried by the sensor, coagulation of the fluid, corrosivedeterioration caused to the sensor by direct contact with the fluid,fluid loss from the vessel, or physical damage to the flexible vesselthat contains the fluid.

These considerations have particular applicability to the measurement ofarterial blood pressure of human (or other animal) patients or subjects.In practice, invasive pressure monitoring generally entails a surgicalcut-down and arterial penetration using a hypodermic needle (cannula)through which pulsatile fluidic forces attributable to arterial bloodflow are routed to a suitable pressure transducer. However, variousmedical health care risks associated with invading the human body, suchas clotting, infection, emboli obstructions to flow, and/or major bloodloss generally limit the use of invasive blood pressure monitoringsystems to the most critical of acute care hospital patient monitoringsituations. To minimize these risks, invasive monitoring is almostalways used in conjunction with intravenous application of fluids to thepatient. Disadvantageously, the various fluidic, mechanical andelectrical components generally used in invasive systems are not onlycomplex and fragile, but also require specialized calibration beforeuse, as well as frequent surveillance by specially qualified staff. Inspite of this surveillance, invasive systems often do not remaincalibrated during prolonged periods of use and, as a result, oftenproduce inaccurate and potentially misleading patient blood pressuremeasurements.

Consequently, over the years several techniques have been developed fornon-invasive arterial blood pressure measurement. In general, thesetechniques rely upon attaching an inflatable cuff around an extremity(limb), which is typically an upper arm, of a human patient. Onceattached, the air pressure existing within the cuff is increased to avalue commonly referred to as "suprasystolic," i.e., a pressure inexcess of that minimally necessary to completely occlude a major arteryexisting within the extremity and situated near its surface. Thereafter,blood pressure is most commonly estimated by detecting well-known"Korotkoff" sounds using a stethoscope, a microphone, or an ultrasonicdetector placed on the limb near the artery. These Korotkoff sounds areproduced by the artery and, more particularly, by disturbances in thearterial blood flow due to partial occlusions of the artery caused bythe externally applied cuff pressure. As the cuff pressure decreases andthe extent of occlusion is reduced, various classic phases of soundchange are usually heard until the artery is no longer occluded by anyappreciable amount. Specifically, as the cuff pressure is reduced fromsuprasystolic, the maximum value of pulsatile blood pressure commonlyreferred to as systolic pressure, is usually taken to be equal to thecuff pressure at the time the first Korotkoff sound is detected.Thereafter, the minimum or so-called "diastolic pressure" value ofpulsatile arterial pressure is usually identified in conjunction withthe occurrence of one of two other Korotkoff phases: either theso-called fifth phase when silence occurs or the so-called fourth phasewhich corresponds to a cuff pressure of about 5-10 mm(Hg) higher thanthat occurring at the fifth phase. Manual pressure readings for systolicand diastolic are determined by identifying each desired phase, and, asthe cuff pressure continually decreases, simultaneously noting the scalevalue in mm(Hg) that corresponds to the height of a mercury column (orthe pointer on an aneroid guage) which is pneumatically connected to thecuff air pressure. Devices of this sort are commonly referred to as"sphygmomanometers."

Unfortunately, the accuracy of any non-invasive sphygmomanometer typeblood pressure measurement system, typified by that described above, islargely dependent on the skill and hearing acuity of its user indetecting the rather subtle sound changes (such as the very gradualtransition to silence after the fourth phase occurs), and,simultaneously therewith, determining the exact level of the mercurycolumn. In addition, dexterity, sensory limitations and inexperience ofthe user; interference of environmental noises, and the need tofrequently calibrate the measurement system often occur and allcontribute to produce highly inconsistent results. This inconsistency isa widely known characteristic of sphygmomanometric systems.

Consequently, in an endeavour to minimize inconsistent results, manyattempts have occurred in the art to automate the process ofsphygmomanometric measurement. Specifically, these attempts involveusing electronic processing circuitry to automatically determine thedesired phases of Korotkoff sound change and the simultaneouslyoccurring systolic and diastolic cuff pressure values.

These attempts are typified by the systems disclosed in U.S. Pat. Nos.3,581,734 (issued to Croslin et al on June 1, 1971); 4,245,648 (issuedto Trimmer et al on Jan. 20, 1981) and 4,271,844 (issued to Croslin onJune 9, 1981). Each of these three patents discloses a computerizedsphygmomanometer measurement system in which an occlusive cuff isattached around a limb of a patient. The cuff is then inflated, eithermanually or automatically by an electrically driven air pump which iscontrolled through either a computer or a hard-wired digital circuit. Ineach of these systems, the cuff is inflated to a suprasystolic occludingpressure prior to taking (sampling) any blood pressure measurement data.Then, by automatically undertaking various detection and determinationprocesses, as well as deflating (bleeding-down) the occlusive cuff,these systems attempt to eliminate many of the above-described manualsteps that can cause measurement error in manual sphygmomanometersystems known to the art. Unfortunately, these automatedsphygmomanometer systems are incapable of reliably and consistentlyrepresenting the true status of blood pressure, in the same manner asprovided by direct invasive monitors that are widely accepted as the"standard of blood pressure measurement accuracy".

Specifically, sphygmomanometer systems commonly producemisrepresentative results due to a number of factors that are generallytransparent to or incapable of being compensated by the practioner-user.One such factor is the impracticality of causing the pressure of anydeflating occlusive cuff known in the art to be made equal to the truepeak systolic pressure value of any one or more intra-arterial pressurewaveforms such that the measured cuff pressure is an accuraterepresentation of systolic. This impracticality results from the factthat any pulsatile intra-arterial peak pressure value exists for only ashort interval of time, (e.g. usually less than 5% of the time).Inasmuch as the timing of cuff pressure bleed-down is a random variable,the cuff pressure is typically lower than true systolic peak pressure byrandom amounts, e.g., up to 10 mm(Hg), depending on the deflation rateused before the desired Korotkoff or pressure displacement waveformsignal occurs--which indicates when the cuff pressure is to be measuredand designated as the systolic measurement value. A second factor is theapparent lack of any uniform and accurate diastolic determination methodin systems known to the art. Specifically, either one of two Korotkoffphases, i.e., the fourth and fifth pnase, each of which producesconsistently different measurement values have found wide use in priorart systems. Also, these diastolic measurement methods known in the artoften determine diastolic pressure as the value of occlusive cuffpressure whenever it exceeds a certain threshold. Such a threshold valueis primarily dependent on the cuff pressure at the mean arterial bloodpressure instead of other more relevant and accurate independentphysiologic variables. Moreover, these methods are generally premised onan assumed linear relationship existing between amplitude values at meanand diastolic pressure and linearly extrapolate the diastolic pressurevalue based upon the mean pressure value. Accordingly, these measurementmethods have the unfortunate effect of assuming somewhat erroneously,that a single fixed linear elasticity relationsnip defines thestress/strain (e.g. pressure/displacement) characteristics of the arterywalls of all patients for whom blood pressure is to be non-invasivelymeasured--thereby resulting in an inaccurate determination of the truediastolic pressure value. Lastly, a third factor is that systolic anddiastolic pressures commonly vary by differing amounts from oneheart-beat to the next due to several physiologic factors for bothnormal and critically ill patients. Unfortunately, any combination ofthese factors serves to over- or under-state not only the value of bloodpressure, but also more importantly changes in arterial blood pressureoccurring over time between successive measurements taken from any onepatient.

Moreover, these prior art systems not only lack the capability ofaccurately portraying the arterial blood pressure associated withindividual heart-beats, but also disadvantageously they generallyproduce only one systolic and diastolic reading during a measurementcycle that can span between 20 and 100 successive heartbeats. Toproperly represent the true status of blood pressure on a heart-beat toheart-beat basis, a much higher sampling rate is necessary. However, ifany of these sphygmomanometer systems were used to measure arterialblood pressure variations on a continuous heartbeat-by-heartbeat basis,then the occlusive cuff would need to be repetitively and successivelyinflated to a suprasystolic pressure and possibly to atmosphericpressure over many short successive intervals of time, such as, forexample, 10 times per second, as is disclosed in U.S. Pat. No. 4,343,314(issued to Sramek on Aug. 10, 1982). Unfortunately, prevailing medicalopinion is that any patient wearing an occlusive cuff cannot becontinuously subjected to either elevated cuff pressures more than about30% of the time during which the cuff is being worn or repetitivecycling of cuff pressure between suprasystolic and sub-diastolicpressures on the order of more than once every one to three minutes,without experiencing significant discomfort, trauma, and possiblephysiologic damage.

A typical repetitive cycling sphygmomanometer measurement system knownto the art which attempts to minimize patient discomfort is disclosed inU.S. Pat. No. 4,378,807 (issued to Peterson et al on Apr. 5, 1983). Asdescribed therein, a control circuit automatically initiates one cycleof occlusive cuff inflation and bleed-down deflation only after a ratherlong pre-defined interval of time typically on the order of 7.5 to 60minutes has elapsed. Unfortunately, pressure readings (one systolic andone diastolic) are only taken at the conclusion of this relatively longinterval. As a result, the amount of measurement data is insufficient todetermine short and long term trends and variability in blood pressure,as well as to identify, with any degree of reliability, any irregularheart-beat pulsations. Thus, such a system is unsuitable for prolongedcontinuous blood pressure monitoring of the critical patients.Consequently, invasive pressure monitoring systems--even in spite oftheir attendant health risks, as discussed above--are used tocontinuously measure and display the pressure waveform for eachheart-beat and to compute the systolic, diastolic and mean pressurevalues based upon averages of a number (typically 4-6) of successiveheartbeats.

An alternate well-known scheme of non-invasive monitoring involvesmeasuring arterial wall displacement (i.e., radial distension of theartery wall) produced by pulsatile arterial blood pressure and thentranslating the measured displacement into an instantaneous bloodpressure value. These measurements and translations would, if performedat a sufficiently rapid rate, appear to be continuous, i.e. result inthe display of an uninterrupted trend of sequentially-occurring pressurewaveforms showing substantial detail of the pulsatile nature of eachwaveform, much in the same fashion as obtained through an invasivemonitor. See, for example, P. Flaud et al, "Pulsed Flows in ViscoelasticPipes. Application to Blood Circulation", Journal of Physics (France)Vol 35, No. 11, November 1974, pages 869-882 and P. Flaud et al, "AnExperimental Device for Modelling Arterial Blood Flow," Review ofPhysical Applications (France) Vol. 10, No. 2, March 1975, pages 61-67,which disclose that radial displacement of the arterial wall is relatedto intra-arterial blood pressure changes. However, the relativemagnitude of wall displacement is also directly related to theelasticity of the wall of the arterial vessel. Unfortunately, arterialelasticity not only varies significantly from patient to patient butalso varies at different locations along each artery, as well as atdifferent times for the same patient. Thus, a noninvasive pressuremonitoring system that relies on relative arterial wall displacement,requires that its measurements first be calibrated against pressuremeasurements taken by a separate reference device, such as an occlusivecuff, which would then serve as a calibration reference for subsequentpressure values based upon arterial wall displacement measurements.

Hence, in view of the drawbacks associated with prior art non-invasivemeasurement systems, continuous blood pressure monitoring systems knownand used in the art are generally invasive and thus rely on intruding amajor artery of the patient.

SUMMARY OF THE INVENTION

An object of the present invention is to provide a system which cancontinuously and non-invasively monitor the pressure of a pulsatilefluid flowing through a flexible tube.

A specific object is to provide an accurate continuous non-invasiveblood pressure monitoring system which can be attached to a patient andoperated for either relatively brief or substantially prolonged periodsof time without any physiologic risks and/or significant discomfort tothat patient.

Another specific object is to provide such a monitoring system whichgenerates a substantially continuous record of pulsatile blood pressureactivity and associated numeric measurement parameters.

Another specific object is to provide such a system in which itsaccuracy is substantially unaffected by the skill of the user, and forwhich minimal retraining is required for persons already experienced inthe use of available pressure measurement instruments and techniques.

Another specific object is to provide such a system which deflates ablood pressure cuff, through one or more controlled substantially linearrates.

Another specific object is to provide such a system which compensatesthe systolic and diastolic measurements for the affects of hemodynamicvariability thereby producing measurement values that are consistentwith those produced by invasive monitoring systems.

Another specific object is to provide such a system which is entirelyself-contained.

Another specific object is to provide such a system which automaticallyadjusts for a multitude of different, typically non-linear factors suchas variations in arterial elasticity and the types and relative amountsof intervening tissue existent between a patient's artery and anon-occluding pressure sensing cuff.

Another specific object is to provide such a system, which to ensureaccurate consistent measurements, automatically determines whenever,during a period of continuous monitoring, it requires re-calibration andthen effectuates any such re-calibration(s).

Another object is to provide a calibration process which can be used asa basis for calibrated measurement of pulsatile arterial activity, suchas, for example, systolic, diastolic, and mean blood pressure parametersusing many known arterial measurement systems, for durations in excessof a few seconds, and which are typified by non-invasive electricalimpedance and strain gauge plethysmography or invasive perivascularsensing methods (which detect blood flow, volume, or velocity as afunction of various physiologic parameters that may be taken to beproportional to measured variations in intra-arterial pressure).

Another specific object is to provide such a calibration process that iscompatible with other well-known types of sphygmomanometric systems thatutilize an occlusive cuff, including those employing microphones andultrasound flutter principles which detect arterial phenomena asmeasurement signals during semi-occluded blood flow conditions.

Lastly, another specific object is to provide such a system whichutilizes calibration processes of the occlusive cuff to optionallymeasure discrete systolic and diastolic pressures on an intermittentbasis at pre-set time intervals in a similar fashion to other automaticnon-invasive pressure measurement products known in the art.

These and other objects are accomplished in accordance with theteachings of this invention by first undertaking a calibration phase(procedure) comprised of: determining the blood pressure occurring inrelation to various initial conditions of arterial blood flow andascertaining the values of a plurality of coefficients, each of which isassociated with a corresponding term in a pre-defined function thatcharacterizes blood pressure values in relation to arterial walldisplacement; and second, undertaking a continuous monitoring phasecomprised of: continually measuring subsequently occurring arterial wallpressure displacement waveform values, ascertaining each subsequentlyoccurring blood pressure value as the pre-defined function of eachcorresponding measured arterial pressure displacement waveform value,and automatically re-calibrating the system to the patient after theexpiration of a pre-defined but adaptively changeable time or inresponse to the occurrence of any one of a plurality of pre-definedevents. This interval, i.e. the time between the occurrences ofsuccessive re-calibrations, is adaptively changed in accordance with theresults of at least one prior re-calibration and/or whenever significantchanges in the trend of arterial wall displacement values occur.

In accordance with the specific embodiment disclosed herein, twoseparate inflatable cuffs (a relatively high pressure occlusive cuff anda relatively low pressure waveform sensing cuff) are affixed todifferent locations proximately situated to major arteries of one or twolimbs of a patient's body. A computer in conjunction with variouspneumatic components effectuates the process of inflation(pressurization) and deflation of each cuff as well as the dataacquisition from each. Instantaneous arterial blood pressure ischaracterized in terms of a parabolic function of arterial walldisplacement: namely f(x)=ax² +bx, where x is proportional to changes inarterial wall displacement measured from a constant reference value, and(a) and (b) are coefficients having values that primarily depend uponvarious physical characteristics (such as the elasticity of the arterialwall and interspersed biological tissue--existing at the site whereblood pressure is being measured, and the cuff material itself) andvarious blood pressure values determined during the calibration phasethrough use of the occlusive cuff.

Operation of the blood pressure measurement system occurs, viaessentially a two-phase approach. During the first, or "calibration",phase, the computer automatically inflates (pressurizes) the occlusivecuff to a pre-defined suprasytolic value, typically on the order of 150mm(Hg), and also inflates the waveform sensing cuff to a relatively lowpressure of approximately 40 mm(Hg). During this time, the computerautomatically checks the integrity of both cuffs to determine whetherany significant pneumatic leakage exists anywhere in the system andconfirms that both cuffs are properly affixed to the patient. Once bothcuffs have been inflated, the computer causes the pneumatic componentsto bleed down the pressure in the occlusive cuff at a controlled ratewhile maintaining the pressure of the waveform sensing cuff constant ata value of approximately 40 mm(Hg). During this controlled bleed-down,arterial pressure displacement waveform information is sensed throughinstantaneous pressure variations (perturbations) occurring in both theocclusive and the waveform sensing cuffs.

The resulting displacement waveform information from both cuffs isdigitized and resulting sample values are stored by the computer. Thesesamples are then processed, via several different techniques, todetermine systolic and diastolic occlusive cuff pressures, as well asthe values of the coefficients (a) and (b).

The particular methods for determing systolic and diastolic occlusivecuff pressure values adjust for heart-beat to heart-beat variability,random bleed rate errors, and patient movement artifacts. Specifically,both the systolic and diastolic pressure determinations are dependentupon analysis and weighted calculations of two groups of at least fourpressure displacement waveforms which generally occur when the occlusivecuff pressure is at or near true systolic pressure, first, and then truediastolic pressure, second, during bleed-down. Simultaneously therewith,measurements of the same two groups of pressure waveforms are made usingthe constant low pressure waveform sensor cuff. Simultaneously with orshortly after--in the event both cuffs are positioned on one limb ratherthan on opposite limbs) the determination of systolic and diastolicpressure values through occlusive cuff measurements, peak and troughvalues, associated with the sequence of waveforms measured from thewaveform sensor cuff, and averages (denoted as base level values) ofthese peak and trough values are computed. Shortly thereafter, theocclusive cuff pressure is exhausted to ambient (i.e. atmospheric), andthe peak and trough values, the corresponding base level values as wellas the corresponding systolic and diastolic occlusive pressure valuesare all used to determine coefficient values (a) and (b) contained inthe arterial wall displacement/pressure function. After thesecoefficients are determined, the computer uses the displacement/pressurefunction to calculate a set of values for subsequent storage in alook-up table. This table consists of the blood pressure values thatcorrespond to a relatively large number of uniformly-spaced arterialwall displacement values which span an entire pre-defined numeric range.

The second or "continuous" monitoring phase, based on the newlycalculated look-up table, commences immediately upon conclusion of thecalibration phase. During this second phase, data in the look-up tableis used to convert actual arterial pressure displacement waveform samplevalues into blood pressure waveforms for both display and subsequentcalculation of various numeric measurement parameters. Specifically,individual displacement waveforms obtained through the low pressurewaveform sensor cuff are continuously sampled and digitized at arelatively fast rate. The value of each sequentially measuredinstantaneous sample is then used by the computer to access the look-uptable to determine a corresponding instantaneous value of calibratedblood pressure. Since an artifact in the arterial blood flow can induceerrors in blood pressure measurements, each calibrated blood pressurevalue is tested, by determining whether its value lies outside of apre-defined range, in order to identify those values which might havebeen affected by artifacts and are those of questionable accuracy. Thenon-affected values are then used in the computation of variousdisplayed numeric measurement parameters. Simultaneously with thislatter step, each calibrated pressure value is graphically displayed,along with a sequence of immediately prior pressure values, on anamplitude (pressure) vs. time basis. Any pressure values identified asbeing affected by artifacts are specifically labelled in the display,by, for example, being replaced with an appropriately labeled horizontalbar.

All the sequentially produced calibrated blood pressure values aredisplayed at a sufficiently rapid rate such that the resulting displayappears as a continuous trace and accurately represents a patient'scontinuous arterial blood pressure waveform activity, in essentially thesame form as obtained using well-known invasive monitoring techniques.Specifically, the most recently detected and calibrated pressurewaveforms first appear at the beginning of the trace display area,scroll across and then disappear as time passes, while simultaneouslynew waveforms continue to appear at the beginning, all in their actualsequence of occurrence. In addition, displayed measurements of variousnumerical parameters include: systolic, diastolic, mean and pulsepressures (typically, averages of individual values from 4-6 waveforms);variability indices of waveform-to-waveform systolic or pulse pressuresand/or maximum rate of systolic pressure ascent (sometimes termed theendo-cardio-viability ratio); and various heart rhythm measures.Furthermore, many of these numerical measurement parameters are checkedagainst pre-defined minimum and maximum alarm limit values and, when anyof these limits is exceeded, appropriate warning notifications aretransmitted visually and/or aurally to an operator. In addition,historical arterial blood pressure data, trends, and alarm activity aresummarized and/or retained for subsequent statistical processing andpatient hard copy document records.

Since the waveform sensing cuff is only inflated to a relatively lowpressure, it can be advantageously worn quite comfortably by any patientfor an extended period of time. Pressurized air (or another pressurizedfluid) existing within tnis cuff is the medium through which arterialdisplacement activity is transmitted to a pressure transducer. Thismedium enables the externally applied pressure to be readily controlledsuch that it remains essentially constant over time, therebyadvantageously assuring that the pressure displacement waveform samplesare properly referenced to a known "base level" reference pressure.Through on-going repetitive sensing of this reference pressure, i.e. theactual reference pressure existing within the waveform sensing cuff,differences in this pressure from the base level reference pressure thatare larger than a pre-determined differential limit can be readilyadjusted by appropriate cuff inflation or deflation to ensure that theactual reference pressure remains substantially equal to the desiredbase level reference pressure. This effectively prevents erroneouspressure measurements that would otherwise occur from time-to-time dueto gradual and relatively long lasting patient movements, slow leaks inthe waveform sensing cuff and other similar circumstances. Specially,the reference pressure might increase as the result of a sustainedexternally-induced and gradually-applied compressive force applied tothe waveform sensing cuff which might result from patient movement orinadverent repositioning of this cuff to a larger circumferential partof the limb to which it is attached. This reference pressure increasewould erroneously augment the displacement sample values detected fromthe waveform sensing cuff in the absence of corrective deflation of thecuff. Conversely, when the cuff has been inadvertently repositioned to asmaller segment of the limb or is experiencing substantial pressureleakage, the reference pressure would decrease and, in turn, erroneouslyunderstate the magnitude of the detected displacement sample values inthe absence of corrective inflation of the cuff.

Furthermore, the average rate of change in reference pressure is alsomonitored during the "continuous monitoring" phase in order to assureconsistent pneumatic system operation and hence accurate displacementmeasurement. Specifically, after each corrective cuff inflation (ordeflation) occurs, the rate at which the actual reference pressurevaries is determined. Whenever the absolute value of this differenceexceeds a predefined limit, this manifests an error condition typifiedby a significant air leak in the pneumatic system, temperature gradientsin the pressurized air used therein or the like. To eliminate thiscondition, a re-calibration is automatically initiated. If, however,these error conditions continue to occur despite re-calibration, thenthe computer displays an appropriate error message, exhausts both cuffsand shuts the entire system down.

At various predefined but adaptively changing time intervals thecomputer automatically initiates another calibration phase. During anysuch "re-calibration", new values are determined for coefficients (a)and (b). Each new coefficient value is then compared with its respectiveprior value to determine the amount of difference existing therebetween.Based upon the magnitude of this difference, the computer adaptivelydetermines the duration of the time interval for the next continuousmonitoring phase (i.e., before the next successive re-calibrationoccurs). In addition, re-calibrations are automatically initiatedwhenever significant rates of change, as previously described, aredetected in the reference pressure of the waveform sensor cuff orwhenever significant cumulative changes occur in continuously monitoredblood pressure such as, for instance, when the systolic, diastolicand/or any other calculated cardiovascular numeric parameters varies bymore than a pre-defined amount (typically 7 percent) from thecorresponding values determined during the prior calibration phase.

BRIEF DESCRIPTION OF THE DRAWING

The invention may be clearly understood from a consideration of thefollowing detailed description and accompanying drawing, in which:

FIGS. 1A and 1B together depict a block diagram of a non-invasive bloodpressure measurement system embodying the teachings of the presentinvention and the manner in which it is attached to a human patient;

FIG. 2 depicts a sketch of Waveform Sensing Cuff 30 shown in FIG. 1A;

FIG. 3 depicts a cross-sectional view of Waveform Sensing Cuff 30 takenalong lines 3--3 shown in FIG. 2;

FIG. 4 depicts a block diagram of Signal Conditioner 147 shown in FIG.1B;

FIGS. 5A and 5B together depict block diagrams of alternativeembodiments of Bleed Rate Control 144 shown in FIG. 1B;

FIG. 6 depicts a sketch of a typical pressure waveform detected duringbleed-down of occlusive cuff 20 shown in FIG. 1A;

FIGS. 7A and 7B depict a flowchart of the overall calbration andcontinuous monitoring operations of the non-invasive blood pressuremeasurement system shown in FIGS. 1A and 1B;

FIG. 8 depicts a flowchart of Cuff Operations Routine 620 referred to inFIG. 7A;

FIG. 9 depicts a flowchart of Cuff Integrity Verification Routine 737shown in FIG. 8;

FIGS. 10A and 10B depict flowcharts of Waveform Sensing CuffPressurization Routine 744a and Occlusive Cuff Pressurization Routine744b, respectively, both referred to in FIG. 8;

FIG. 11 depicts a flowchart of Occlusive Cuff Measurements Routine 630referred to in FIG. 7A;

FIGS. 12A-12G together depict a detailed flowchart of SystolicDetermination Routine 1020 referred to in FIG. 11;

FIGS. 13A and 13B together depict a flowchart of Pulse WindowInterrogation Routine 1250 referred to in FIGS. 12A-12G;

FIG. 14 depicts a flowchart of Systolic Pressure Intercept Routine 1300referred to in FIGS. 12A-12F;

FIGS. 15A-15D graphically depict four hemodynamic sequences ofintra-arterial pressure waveforms with each dashed line representing adifferent bleed-down sequence for occlusive cuff 20;

FIGS. 16A-16H graphically depict, on a pressure v. time basis, theresulting measurements taken through occlusive cuff 20 of eachparticular pressure waveform amplitude sequence that corresponds to eachdashed line bleed-down sequence depicted in FIGS. 15A-15D;

FIGS. 17A-17H are vector diagrams illustrating the determination ofsystolic pressure for each case shown in FIGS. 15A-15D and in FIGS.16A-16H, respectively;

FIGS. 18A and 18B are flowcharts of Mean Profile Routine 1033 referredto in FIG. 11;

FIG. 19A is a sketch of a typical pressure waveform sensed by OcclusiveCuff 20 depicting the systolic, mean and diastolic pressures associatedtherewith;

FIG. 19B is a sketch of a typical sequence of pressure waveforms--one ofwhich is shown in FIG. 19a--sensed through Occlusive Cuff 20 during itsbleed-down;

FIGS. 20A and 20B are flowcharts of Sliding Slope Routine 1037 referredto in FIG. 11;

FIGS. 21A-21F graphically depict six different illustrative sequences ofpressure waveform peaks and show the determination of the diastolicpressure (DP) for each sequence by Sliding Slope Routine 1037; and

FIG. 22 depicts a flowchart of Diastolic Validation Routine 1040 shownin FIG. 11.

To facilitate easy understanding, identical reference letters and/ornumerals are used to denote identical elements common to the figures.

DETAILED DESCRIPTION

Although the teachings of the present invention are applicable tocontinuous non-invasive pressure measurement of any relativelynon-compressible fluid, for purposes of the following description, thepresent invention will be described in terms of a continuousnon-invasive blood pressure measurement system. In this respect, allpressure values recited hereinafter are in millimeters of mercury, i.e.mm(Hg).

1.0 Hardware Considerations

A non-invasive blood pressure measurement system (hereinafter referredto as "the system") embodying the teachings of the present invention isshown in block diagram form in FIGS. 1A and 1B. These figures also showthe manner in which the system is typically attached to a human patient.

As shown, the system is essentially comprised of control and measurementunit 100 and two inflatable cuffs: occlusive (high pressure) cuff 20 andwaveform sensing (low pressure) cuff 30. These cuffs are preferablysecured around opposite limbs of patient 5 and are automaticallyinflated and deflated, i.e. bled-down, by control and measurement unit100 which also, in a manner to be fully described below, senses arterialwall displacement and calculates the instantaneous blood pressure valuescorresponding thereto.

Both cuffs are connected by respective pneumatic lines (tubing) tocontrol and measurement unit 100. Lines 21 and 31 are respective inletlines to occlusive cuff 20 and waveform sensing cuff 30, and pneumaticlines 23 and 33 are respective outlet lines from these same cuffs. FIG.1a shows the preferred manner in which these cuffs are secured to thepatient, i.e. with occlusive cuff 20 attached around upper arm 51 andwaveform sensing cuff 30 attached around upper arm 52, such that thecenter of the air bladder of each cuff is proximately situated to themajor (brachial) artery in each arm. A variety of alternate patientattachment schemes are also possible with the system. For example, sinceat least two preferred sites exist on each limb, e.g. the upper arm andwrist of the same arm or the thigh and ankle of the same leg, the twocuffs may be positioned on any one or two of a patient's four limbs. Aswill be apparent from the discussion below, the system is capable ofaccurately performing continuous monitoring even if occlusive cuff 20 ispositioned at the upper location (on an arm or thigh) and waveformsensing cuff 30 is positioned at the more distal location (wrist orankle) of the same limb. Generally, the embodied teachings of thepresent invention apply to all these alternate schemes, but in thelatter situation where both cuffs are attached to the same limb,continuous monitoring must be interrupted for pre-determined,illustratively half-minute, intervals during which re-calibrationoccurs. This interruption is necessary since an inflated occlusive cuffdistorts (occludes) the pulsatile arterial blood flow that wouldotherwise be detected by the waveform sensing cuff if it were located onanother limb.

Within control and measurement unit 100, computer 200 controls theinflation and deflation of both cuffs, as well as the data acquisitionfrom within each. Computer 200 is illustratively comprised of any one ofseveral well-known processors and is advantageously implemented usingany one of many commercially available microprocessors along withnecessary and ancillary support circuitry. Since the architecture of thecomputer system is immaterial for purposes of the present invention,this architecture, for purposes of clarity, is illustratively shown ashaving only a single data and address bus 210. This bus inter-connectsvarious input-output (I/O) ports, namely ports 201, 203 and 216; centralprocessing unit (CPU) 213, random access memory (RAM) 212; read onlymemory (ROM) 211, timer and time-of-day clock 204; and communicationscircuitry comprised of keyboard controller 205, CRT controller 214, andcommunication interface 215. ROM 211 stores the program, which asdiscussed in much greater detail below, controls the operation of thesystem, and the data processing used therein. RAM 212 stores temporarydata. Under control of the CPU and the program stored in ROM 211, thesystem accepts control information from an operator through,illustratively, keyboard 160 and keyboard controller 205, and providesoutput information compatible for display on a video terminal, throughCRT controller 214, or in a form illustratively RS-232 compatible, viaport 232, for connection to other digital devices, such as a hardcopyrecorder, another monitor, or a centralized computer system. CRTcontroller 214 illustratively includes a frame-store memory for use inproducing graphics, including historical blood pressure trend data, forsubsequent display on video monitor. Input information, including dataand commands, can also be applied to the computer in serial form viabi-directional port 232 and communication interface 215. Lastly, timerand time-of-day clock 204, which is connected to bus 210, provides atiming function, as well as a real-time clock for use by computer 200 inaccordance with the program stored in ROM 211.

Computer 200 also provides, through the I/O ports, appropriateelectrical signals to control the operation of the pneumatic elementscontained within the system, as well as to control the sampling of datafrom both cuffs. Through I/O port 203, CPU 213 obtains pressure data indigital form from analog/digital converters 157A and 157B. The CPU,through I/O port 216, drives various alarms and other indicators todisplay the current status of the system. I/O port 201 providesappropriate electrical signals on leads 161, 163, 165, and 167 to pumpcontrol 141, bleed rate control 144, and electrically-operated pneumaticvalves 111 and 113, respectively, to control the inflation and deflationof both cuffs.

To inflate either cuff, computer 200 first applies appropriate voltagelevels, via I/O port 201 and leads 165 and 167, to activate pneumaticvalves 111 and/or 113 such that the desired cuff(s) is pneumaticallyconnected through pneumatic lines 119 and/or 123 to manifold 118.Manifold 118 serves as a reservoir for the compressed air generated byair pump 121 and as an inter-connection point for the differentpneumatic components used in the system. Once the appropriate valve(s)has been activated, computer 200 then, via I/O port 201, applies anappropriate voltage, via lead 161, to cause pump control 141 to activateair pump 121. Specifically, pump control 141 converts the digital levelon lead 161 into an appropriately-scaled and buffered analog voltagewhich is then applied, via lead 127, to air pump 121. This pump appliescompressed air, at a pressure determined by the magnitude of the voltageappearing on lead 127, through pneumatic line 120 to manifold 118 and,in turn, through the activated valve(s) 111 and/or 113, to tne selectedcuff(s). Valve 111, when activated, routes all or a portion of this airvia pneumatic line 21 to occlusive cuff 20, and valve 113, whenactivated, alternatively routes all or a portion of this air viapneumatic lines 31 to low pressure waveform sensing cuff 30. Clearly,many other configurations of pneumatic components, which togetherperform the same function as that described above, can be readilysubstituted for the configuration shown in FIGS. 1A and 1B.

To sense the air pressure contained in either one or both of the cuffs,computer 200 first selects the appropriate input signal to be convertedby each A/D converter, i.e. converters 157A and 157B. Specifically, eachA/D converter receives an analog signal which is first produced by thepressure transducer connected to each cuff and subsequently conditionedby an appropriate signal conditioner. Computer 200, by applyingappropriate select signals, via I/O port 201, and leads 162 and 164causes each of the A/D converters 157A and 157B, respectively, to selectthe desired input signals for subsequent conversion. For example, eitherof A/D converters 157A and 157B can select the analog signals associatedwith either occlusive cuff 20 or waveform sensing cuff 30.Alternatively, if these converters contain appropriate bus-compatibleaddressing circuitry, then the selection signals are applied over thebus as addresses thereby eliminating the need for separate selectionlines, such as 162 and 164. With either arrangement, the performance ofeach A/D converter can advantageously be checked, particularly forpurposes of calibration, by switching (reversing) the pressuretransducer output signals which are converted by each A/D converterand/or by selecting a fixed reference voltage (+V_(REF) or -V_(REF)) forconversion by either or both A/D converters.

The output of pressure transducers 133 and 136, associated witnocclusive cuff 20 and waveform sensing cuff 30 respectively, isamplified, scaled and appropriately filtered by signal conditioners 147and 149. The circuitry of each conditioner is identical, and that ofillustratively conditioner 147 is shown in block diagram form in FIG. 4.Each conditioner produces three separate output signals Pw, Prs, and Pr.As shown, conditioner 147 imparts a pre-determined low-passcharacteristic to the output of its associated pressure transducer tofilter out high frequency noise and other preturbations from the desiredlow-frequency data. In particular, pressure displacement waveform analogsignal Pw is produced by routing the output of transducer 133 firstthrough high pass filter (HPF) 147a and then through low pass filter(LPF) 147b, which have 3 dB attenuation value cut off frequencies ofabout 0.2 and 20 Hertz, respectively. Additionally, analog signal Prs,which consists of a slowly varying respiratory-induced pressuredisplacement component Pr plus a steady-state cuff pressure value, isproduced by routing the output of transducer 133 through LPF 147c whichhas a 3 dB attenuation value cut-off frequency of about 0.4 Hertz.Capacitive coupler 147d extracts the analog signal component Pr fromsignal Prs. In the preferred embodiment shown, both analog signaloutputs Prs and Pr are connected to A/D converter 157B, and analogsignal output Pw is connected to A/D converter 157A.

Once the appropriate input signal has been selected for each A/Dconverter, computer 200 (See FIG. 1B) then applies a "START CONVERSION"signal, via lead 159, to each A/D converter, to initiate conversion ofits selected input signal. After a short pre-defined period of time haselapsed, i.e. sufficiently long for the converter to convert the datainto digital form and to allow the data to stabilize on bus 158, I/Oport 203 transfers the digital data into the computer for furtherprocessing.

The deflation (bleed-down) of either cuff requires that the desired cuffbe selected and a pneumatic air channel be established between it andbleed valve 124. To set the rate at which air is bled from the selectedcuff, computer 200 first applies an appropriate level toelectrically-operated pneumatic valves 111 or 113, via leads 165 or 167,respectively, to select the appropriate cuff and route the compressedair contained therein to manifold 118, via pneumatic lines 119 or 123,respectively. Thereafter, computer 200, via I/O port 201 and leads 163,provides appropriate signals to bleed rate control circuit 144 whichspecifies the rate at which air is bled (the "bleed-rate") from theselected cuff and exhausted to the atmosphere via bleed valve 124.

A block diagram of one embodiment of bleed rate control 144 is shown inFIG. 5A. As shown, an incoming 8-bit word, from I/O port 201, whichspecifies the bleed rate, is loaded into variable rate counter 144b inresponse to a load pulse (not shown). Thereafter, clock 144a applies atrain of clock pulses, to the clock input of this counter torepetitively increment its contents by one. The most significant bit(MSB) is applied through buffer 144d, to drive bleed valve 124. As longas the value of the MSB is one, buffer 144d produces a high output level(e.g. a "1") to open the bleed valve. Alternatively, whenever the valueof the MSB is zero, buffer 144d produces a low (e.g. a "0") level signalto close the bleed valve. As soon as the count "rolls over" from itsmaximum count to zero, the bleed rate value is re-loaded into thecounter and incrementation begins again. Counter 144b is advantageouslyfabricated as a latched counter in which the bleed rate value is writteninto an input latch and a carry out pulse from the counter is used toload the contents of the latch into the counter at the occurrence ofevery "roll over". Hence, the magnitude of the bleed rate value linearlyspecifies the open-time (and duty cycle) of bleed valve 124. Severaldifferent 8-bit bleed rate values are stored as constants withincomputer 200 so as to define a number of different linear rates for usein conjunction with different phases of occlusive cuff measurementand/or different cuff sizes. A particular one of these constants isselected by the program resident within ROM 211 and applied via I/O port201 and leads 163 to bleed rate control 144.

An alternate embodiment for bleed rate control 144 is shown in FIG. 5B.In this embodiment, computer 200 provides various control signals, viaI/O port 201 and leads 163, to step motor controller 144f which, inturn, controls the incremental movement of the armature of step motor144g. This armature is mechanically connected, through illustratively awell-known rack and pinion assembly or the like (not shown), to needle124a to vary its longitudinal position within valve body 124b, therebydetermining the orifice size of the valve. In operation, computer 200,via leads 163, applies a signal of appropriate level to the directioninput of step motor controller 144f in order to set the direction inwhich the armature of step motor 144g is to turn, i.e., to push theneedle into the valve body, thereby closing the valve, or to pull theneedle from the valve body thereby opening the valve. Thereafter,computer 200 applies a series of clock pulses to the clock input of stepmotor controller 144f to incrementally move the needle in order tolinearly open or close the valve by a desired amount. This, in turn,sets the bleed-rate accordingly. The rate of these clock pulses isgoverned by the desired rate of change in the bleed rate. Whenever anappropriate signal is applied to the clear input by computer 200, eitherduring system operation or during "power-up", step motor controller 144fcauses step motor 144g to move to a pre-selected initial position, i.e.to fully open the valve for safety purposes.

The occlusive cuff, in a manner to be described in detail shortly, isonly used during a relatively brief and infrequent "calibration" phaseto obtain systolic and diastolic blood pressure values of the patient.Both these values are obtained during bleed down of this cuff from the"supra-systolic" pressure. At a point while the air pressure in thiscuff is bled down from this initial maximum pressure, pulsatile arterialblood begins to flow through the then partially occluded artery, thus,imparting a train of pressure displacement waveforms to the linearlydecreasing pressure of the air contained within the occlusive cuff. Atypical pressure waveform produced by one heart-beat is depicted in FIG.6. As shown, the air pressure in the occlusive cuff is being bled-downalong a line generally resembling line X-Y. At illustratively pressureP₁, the arterial wall begins to distend, i.e. move radially outward, inresponse to the onset of a pulse of blood flowing through the artery. Asthe artery continues to distend outwardly, it exerts pressure onto theocclusive cuff and produces a pressure displacement waveform havingamplitude values PWA (equaling P_(A) minus P₂) at time T_(P). The nextpressure waveform illustratively begins at occlusive cuff pressure P₃,which is a lower applied cuff pressure than that occurring at the onsetof the previous pressure pulse by the amount of air bled-down from theocclusive cuff during this heart beat. A typical complete series ofthese pressure waveforms occurring during a complete measurement cycle,i.e. controlled deflation from supra-systolic to less than diastolic, isillustratively shown in FIG. 19B.

Occlusive cuff 20 is not described in detail since it is preferably astandard "Velcro" wrap-around occlusive blood pressure cuff well knownto those skilled in the art of sphygmomanometer based blood pressuremeasurement.

FIG. 2 shows a side perspective view of (low-pressure) waveform sensingcuff 30, and FIG. 3 shows a cross-sectional view taken through lines3--3 shown in FIG. 2. This cuff is comprised of chamber 300 having fiverigid surfaces (of which only top surface 301, and side surfaces 304,306 and 308 are shown) and a compliant bottom surface 311. All the rigidside surfaces are illustratively metallic or hard plastic with thebottom surface being either soft plastic or rubber. Nipples 307 and 313pneumatically connect air 321 contained within the chamber to pneumaticlines 31 and 33, respectively. To secure this cuff around a patient'sarm (as shown in FIG. 1A), the chamber is illustratively secured to abracelet or strap having arms 303 which are each connected to respectivesides of clasp 305. Each arm is attached illustratively by rivets, suchas rivets 302, to a respective side surface of chamber 300, such assurface 308. Ridges 325, located at opposite ends of the bottom ofchamber 300 serve to advantageously minimize the effect of anydownwardly directed external forces inadvertently applied to top surface301 from interfering with the movement of compliant member 311 caused bypulsatile pressure displacement activity of an underlying major artery.These forces can occur through inadvertent contact with an object orclothing.

In operation, the waveform sensing cuff is first attached around apatient's arm. Thereafter and upon receipt of an appropriate instructionfrom the operator, computer 200 causes the air pump to inflate thewaveform sensing cuff to approximately 40 mm and to thereafter maintainthis pressure. The radial movements (displacements) of the wall of theartery attributable to a heart contraction-induced intra-arterial bloodpressure pulse (herein termed a "pressure waveform") are transferredthrough the patient's skin to the bottom surface of the waveform sensingcuff. These arterial wall displacements, in turn, compress air 321contained within the cuff, and thus in turn modulates the cuff pressurein direct proportion to the magnitude of the arterial wall displacement.A complete cycle of these variations which resembles a pulse and occursat each heart-beat, results in what is hereinafter referred to as a"pressure displacement waveform". During the "continuous monitoring"phase, only the (low pressure) waveform sensing cuff is used to acquirethese waveforms; the (high pressure) occlusive cuff remains completelydeflated during this time. Because the waveform sensing cuff is inflatedto and maintained at a considerably lower pressure than that needed tocause any occlusion to the artery, the waveform sensing cuffadvantageously can be worn continuously by the patient for prolongedperiods of time without causing physiologic damage or any noticeablediscomfort to the patient.

2.0 Software Considerations

Up to this point the discussion has centered on the specific hardware ofthe inventive blood pressure measurement system. With reference to FIGS.7-22, the remaining discussion will now describe the software used tocontrol the operation of the system and, specifically, the dataaquisition, analysis and measurement processes associated therewith.

2.1 Overview--Calibration and Continuous Monitoring

A flow chart of the overall operation of the inventive system isdepicted in FIGS. 7A-B. Whenever the operator depresses a "start" key(not shown) on keyboard 160 (see FIG. 1B), computer 200 automaticallyinitializes itself by executing initialization routine 610. This routineloads various default values from ROM memory into RAM memory andautomatically executes various diagnostics to confirm that the entiresystem is operating properly. Thereafter, as shown, system operation isdivided into two distinct phases: the "calibration" phase and the"continuous monitoring" phase.

The "calibration" phase is comprised of cuff operations routine 620,waveform sensor initialization and occlusive cuff measurements routine630, and moduli look-up determination routine 640. Upon entering the"calibration" phase from the initialization routine, computer 200 firstexecutes cuff operations routine 620. During this routine, the systemautomatically inflates both the occlusive and waveform sensing cuffs topre-defined pressures that are determined by this routine. Concurrentlytherewith, the computer checks the integrity of both cuffs for leaks orimproper installation on the patient. In the event, any leaks arediscovered or if the system determines that either cuff has beenimproperly installed, both cuffs are immediately vented to theatmosphere and an appropriate user notification message is displayed,all as discussed in more detail later in conjunction with the cuffintegrity verification routine shown in FIG. 9. Alternatively, if noleaks are detected and both cuffs are determined to be properly securedto the patient, then waveform sensor initialization and occlusive cuffmeasurements routine 630 is executed.

Waveform sensor initialization and occlusive cuff measurements routine630 determines the base-level reference pressure of the waveform sensingcuff--thereby providing a proper reference for subsequent continuousmonitoring, diastolic and systolic pressures from bleed down of theocclusive cuff and certain base-level peak and trough values associatedwith several pressure displacement waveforms that occur during occlusivecuff bleed down. After the base-level pressure has been determined,routine 630 causes the pneumatic system to bleed air down from theocclusive cuff. Simultaneously therewith, this routine determines thesystolic and diastolic occlusive cuff pressure values of the patientthrough processing pressure displacement waveforms that have beendetected through perturbations in the air pressure of the occlusive cuffwhile it is being bled-down. Once the diastolic and systolic pressurevalues have been ascertained, then the remaining cuff pressure isabruptly reduced to atmospheric and control proceeds to moduli tabledetermination routine 640.

Routine 640 uses both the systolic and diastolic occlusive cuff pressurevalues and base-level peak and trough displacement values, alldetermined in routine 630, as boundary conditions and values of theindependent variable x, respectively, to determine, through solving aset of simultaneous equations, the values of various coefficients,specifically coefficients (a) and (b), which appear in a pre-definedrelationship, illustratively parabolic and of the form f(x)=ax² +bx.This relationship characterizes any instantaneous blood pressure valuef(x) in terms of any pressure displacement sample value x. Once thesecoefficients are calculated, computer 200 fabricates a look-up table ofcalculated blood pressure values for a pre-selected series of close anduniformly-spaced arterial pressure displacement values which span theentire range of displacement values that can be expected to occur duringcontinuous monitoring. This range extends above and below the base-levelpeak and trough values, respectively, by an amount equal toapproximately 25% of each respective value. Once both of thesecoefficients have been determined, each pre-selected displacement valueis successively substituted into the pre-defined relationship in orderto compute each corresponding instantaneous blood pressure value. Theresulting table is stored in RAM memory 212 (see FIG. 1B) existingwithin computer 200 for use during the second, i.e. "continuousmonitoring", phase of system operation.

Once the look-up table has been completely fabricated, the "continuousmonitoring" phase begins with the execution of waveform sensormonitoring routine 650. This routine determines the continuouslyoccurring instantaneous displacement waveform sample values detectedfrom waveform sensing cuff measurements and ascertains the continuousblood pressure measurements corresponding thereto. Specifically, themagnitude of each displacement value detected through the waveformsensing cuff is used to access the look-up table for a correspondinginstantaneous blood pressure value. If the actual displacement valuelies between two adjacent pre-defined displacement values in the table,then the two corresponding blood pressure values stored in the table areinterpolated, using preferably well-known linear interpolationtechniques, to compute the appropriate calibrated blood pressure valuecorresponding to the actual displacement value. Thereafter, computer 200routes each calibrated instantaneous blood pressure value in sequencealong with previously determined calibrated blood pressure values, viaport 231 (see FIG. 1B) to a video terminal for display and a continuoustrace and/or via port 232 as serial digital information to anotherdigital device. These continuous pressure values are applied to theseports at a rate of approximately 50 or more values per second such thatthe displayed result is a continuous trace. To provide a trace similarto the waveform display of an invasive monitor, enough prior values toencompass the last 4-8 seconds of arterial activity are sent to theseports and displayed.

After a pre-defined time interval of continuous monitoring has elapsed,or other events occur such as significant changes in reference pressureor blood pressure parameter levels both of which are recognized bydecision routine 660, the system automatically re-enters the"calibration" phase to re-calibrate its measurements. During any such"re-calibration", new values are determined for coefficients (a) and (b)as well as for diastolic, systolic, base-level reference and base-levelpeak and trough values. Each new coefficient value is then compared withits respective prior value--determined during execution of the mostrecent calibration phase. The amount of difference existing betweencorresponding coefficient values is used to determine the duration ofthe time interval of the next successive continuous monitoring phase.Specifically, if this difference is within an acceptable limit,typically on the order of a few percent of the previous coefficientvalue, the duration of next continuous monitoring phase is set to lastapproximately twice that of the prior continuous monitoring timeinterval. Conversely, if the difference is greater than the acceptablelimit, the computer sets the duration of the next continuous monitoringinterval to approximately half that of the prior interval. The length ofthe interval between successive "re-calibrations" continues toadaptively change until either a minimum pre-defined interval, on theorder of a few minutes, or a maximum pre-defined interval, on the orderof approximately 30 minutes to an hour or more, is reached betweensuccessive "re-calibrations". Moreover, the value of this interval isunaffected by the other aforementioned events, such as significantchanges in blood pressure measurement levels, which by themselves serveto initiate a re-calibration at an earlier time during the continuousmonitoring phase, i.e. prior to the planned end of the current interval,than would otherwise be the case.

If, however, decision block 660 determines that a "re-calibration" isnot to occur, then the system remains in the "continuous monitoring"phase and waveform sensor monitoring routine 650 is merely re-executed.

2.2 Cuff Operations Routine 620

A flowchart of cuff operations routine 620, which forms part of FIG. 7A,is depicted in FIG. 8. Execution of this routine begins with adetermination by decision block 705 as to whether prior continuousmonitoring has occurred for the present patient. If no such monitoringhas occurred, i.e. this is the first pass through the inflation routinefor the present patient, then execution proceeds down the "No" path fromdecision block 705 to decision block 710. This latter decision blockselects an appropriate tentative target occluding pressure value for theocclusive cuff, either about 10 mm(Hg) in excess of the upper systolicpressure alarm alert value--if any--set by the operator (value TP2) or apre-defined default value stored in ROM which is approximately 140mm(Hg)--(value TP1). User accessable panel switches (not shown) are themeans by which the alarm alert values are set by the operator. Executionblock 730 selects the target occluding pressure to be the larger of thetentative target pressures of blocks 720(TP1) and 725(TP2).Alternatively, if prior continuous monitoring had already occurred, thenexecution proceeds down the "Yes" path from decision block 705 toexecution block 715 which sets the "target" pressure to be a value equalto approximately 20 mm(Hg) higher than the average of a pre-determinednumber of prior systolic pressure values determined during the mostrecent monitoring phase. Once the target pressure has been set to theappropriate value by execution of blocks 715 or 730, then control passesto block 735 which initiates the inflation of the occlusive and waveformsensing cuffs. Execution of block 735 opens valves 111 and 113 andactivates air pump 121.

Periodically during cuff inflation, computer 200 executes cuff integrityverification routine 737 to determine whether any air leaks occur and/orwhether both cuffs are properly secured to the patient. This routine isshown in flowchart form in FIG. 9. Upon entry into this routine,computer 200 first executes block 905 to determine the actual pumpingrate, Δp, associated with each cuff at various pre-defined timesoccurring early in the pressurization (i.e. before the pressure in eachcuff reaches 40 mm(Hg)). This rate is illustratively determined byascertaining the differential cuff pressure between the beginning andend of a pre-defined elapsed interval of time and dividing the latterinto the former. Once an actual pressurization rate is determined, apreviously-determined look-up table is accessed through the execution ofblock 910. This table consists of minimum and maximum acceptablepressurization rates ΔP for the waveform sensor cuff and for eachdifferent permissible occlusive cuff size. If the value of the actualrate ΔP lies between a pair of stored minimum and maximum values of ΔP,then the computer, through block 910, characterizes that channel interms of the corresponding type and size of cuff connected thereto, e.g.occlusive cuff channel or waveform sensor cuff channel, and designateseach channel as such and checks to see that both channel designationsare consistent with those produced during the most recent re-calibrationphase. If so, then execution proceeds, via the "yes" path, out of cuffchannel verification routine 737 to path 739 (in cuff operations routine620--see FIG. 8) wherein control is effectively split in order toessentially execute two relatively slow processes simultaneously and inreal-time, i.e. continued inflation of both the occlusive and waveformsensing cuffs. Specifically, control proceeds to both waveform sensingcuff pressurization routine 744a and occlusive cuff inflation routine744b. Although the sequential nature of the computer only permits it toexecute one instruction at a time, the extremely high speed at whichexecution occurs relative to the system process being controlled (cuffinflation, waveform sampling, etc.) permits several such processes to beevoked and controlled in real-time or an essentially simultaneous basis.For purposes of simplicity, the flowcharts have been drawn, using asymbol typified by that shown for path 739, to show simultaneous controlof multiple process rather than to show, from the perspective of thecomputer, the actual sequential operation as evoked by the programstored in ROM 211 (see FIG. 1B).

However, in the event that channel designation is not consistent betweensuccessive re-calibrations, then execution is transferred via the "no"path from block 920, in cuff integrity verification routine 737 (seeFIG. 9), to block 925 which terminates the measurement process andevacuates the pressure in both cuffs. Thereafter, computer 200, viablocks 927 and 929, determines the most probable source of the aberrantpressurization rate(s) and the inability to designate the cuffchannel(s) and in turn displays an appropriate error message.Specifically, execution block 927 subtracts the actual pressurizationrate from the expected pressurization rate (the latter being the mean ofthe minimum and maximum rate) for the undesignated cuff channel to yielda differential pressurization rate, D. The magnitude of D is used byexecution block 929 to access a previously-stored look-up table of faultcondition messages that correspond to all possible configurations ofundesignated channels and ranges of aberrant values of D. Once a messageis selected for a particular situation, it is displayed on the videoterminal. For example, if the actual pressurization rate matches thatrequired for the waveform sensor cuff, but the differentialpressurization rate of the undesignated channel were too excessive to bematched to that associated with any occlusive cuff then the faultcondition message might be "occlusive cuff tubing obstruction."Conversely, for lower-than-expected pressurization rates, "looselyfitted cuff", "detached cuff", "disconnected air line" or "air lineleakage" fault conditions can be identified and displayed, depending onthe resultant value of D.

As noted, upon successful designation of both cuff channels, executiontransfers from block 920 of cuff Integrity Verification routine 737 toevoke two cuff inflation processes essentially simultaneously; namelyinflating the waveform sensing cuff to a constant low pressure ofapproximately 40 mm(Hg) and inflating the occlusive cuff to itsappropriate target (occluding) pressure value. Specifically, aftercontrol is transferred from block 737, execution of Waveform SensingCuff Pressurization Routine 744(a) is initiated. Upon entry in thisroutine, as shown in FIG. 10a, inflation pressures are first measuredand tested by block 740(a) and 741. Valve 111 (See FIG. 1A) ismaintained open until the waveform sensing cuff pressure reaches 40mm(Hg), at which time execution of block 743 causes this valve to close.Once this occurs, control exits from waveform sensing cuffpressurization routine 744a and, as shown in FIG. 8, transfers towaveform sensor initialization and occlusive cuff measurements routine630.

Essentially at the same time that waveform sensing cuff pressurizationroutine 744a is being executed, to occlusive cuff pressurization routine744b, shown in detail in FIG. 10B is also being executed. Upon entryinto this routine, decision block 747 first measures the occlusive cuffinflation pressure and, in response thereto, determines whether thispressure equals the target pressure that was previously determined inblock 715 or 730. If not, block 745 is executed to continue occlusivecuff inflation. When the actual occlusive cuff pressure equals thetaught pressure, control is passed, via the "Yes" path from decisionblock 747 to block 750 which discontinues cuff inflation byde-activating air pump 121. Thereafter, execution proceeds to decisionblock 755 to determine if the then existing occlusive cuff pressure issufficient to occlude arterial blood flow, i.e. whether this pressure isat a "suprasystolic" value.

Specifically, routine 755 monitors (samples) the air pressure in theocclusive cuff over a duration of approximately 2 to 3 seconds for anyperturbations attributable one or more pressure waveforms, as depictedin FIG. 5. If any such waveforms are detected, decision block 760 isfirst executed to determine whether the then existing occlusive cuffpressure is outside a pre-determined range, specifically higher than theaverage systolic pressure determined during the most recent continuousmonitoring interval +75 mm(Hg) or greater 265 mm(Hg). In the event, theactual occlusive cuff pressure is too large, i.e. larger than either ofthese two measures, an error condition occurs. Control is thentransferred to block 770 which dumps pressure in both cuffs. Inasmuch asthe error condition may be due to an isolated and transient cause, block770 re-initiates cuff inflation by transferring control to the beginningof cuff operations routine 620. If however, the error continues for asecond time, then block 773 is executed which dumps the pressure in bothcuffs, displays an appropriate error message and then shuts the systemdown. Alternatively, if the occlusive cuff pressure is below the twomeasures specified in decision block 760, then block 765 is executedwhich results in increasing the applied occlusive cuff pressure byapproximately 20 mm(Hg). The occlusive cuff pressure keeps increasing in20 mm(Hg) increments until arterial blood flow is completely occluded byapplication of a suprasystolic cuff pressure sufficient to prevent anypressure waveforms from occurring during a continuous 3 second period;thereafter control exits this routine via the "No" path from decisionblock 755. At the instant both cuffs are properly inflated, i.e. afterroutines 744a and 744b have been completely executed, control as shownin FIG. 7A exits from cuff operations routine 620 (FIG. 8) to waveformsensor initialization and occlusive cuff measurements routine 630 (FIG.11). This latter routine is comprised of two portions, routine 633 androutine 636--the former will be discussed in the next section, and thelatter will be discussed in the following section. While these lattertwo routines are in practice executed such that the waveform samplingprocess in each occur nearly simultaneously, these routines are shown assequentially occurring in FIG. 7A merely for purposes of simplifying thefigure and the ensuing discussion.

2.3 Waveform Sensor Initialization and Occlusive Cuff MeasurementsRoutine 630

Upon culmination of the execution of cuff operations routine 620,control is transferred to, as depicted in FIG. 7, waveform sensorinitialization and occlusive cuff measurements routine 630, which isshown in detail in FIG. 11.

2.3.1 Waveform Sensor Initialization Routine 633

Routine 633 consists of determining certain "base-level" values andrelationships that are derived from waveform sensor cuff sample dataacquired during each "calibration" phase. Base-level peak and troughvalues are also computed from the sampled waveform sensor cuff data forsubsequent use in previously-described moduli table determinationroutine 640. Also, this routine determines the actual value of thepreviously described base-level waveform sensing cuff reference pressureand its rate of change. These latter values are used as comparisonstandards throughout the following "continuous monitoring" phase toensure that pressure displacement waveform sample values acquired duringthat phase are properly referenced and thereby accurately detected.

The process by which routine 633 determines the base-level valuesrequires a detailed description of the manner in which the analog outputsignal of pressure transducers 133 and 136 is conditioned prior tosampling. Specifically, as shown in FIG. 4, three analog signalcomponents (Pw, Prs, and Pr) are segregated from a composite analogoutput signal produced by each transducer, illustratively transducer133, prior to sampling and digitization via A/D converters 157A and157B. First, a Pw component, of the pressure displacement waveform, thatvaries at the patient's heart-rate is separated by filtering lowfrequency components from the composite analog signal. The resulting Pwsignal essentially consists of all amplitude values in excess of apressure level that extends between successive waveform trough (minimum)values. This waveform component is similar to that shown in FIG. 6, butas will be made clear below, does not include all components of thepressure displacement waveform, as it referred to in other parts of thisdisclosure. A second analog component, Pr, is a low frequency arterialpressure displacement signal that varies in response to the patient'srespiration cycle. The magnitude (amplitude) of respiratory-inducedarterial displacement cycles are positive and negative relative to acomputed average value (i.e., are sinusoidal in nature) and these valuescan be negligible or quite significant, depending on physiologicconditions of the patient, and common undergo a cyclic change at a rateof every 4-7 heart-beats. The third signal component, Prs, is comprisedof the sum of a static non-varying cuff pressure value of approximately40 mm(Hg), and the above-described Pr component. Essentially, Prs is thecomposite transducer signal (that represents the total waveform sensingcuff pressure) excluding the Pw component.

After the three analog signal components are separated by signalconditioner 147 from the composite output signal produced by transducer133, Pw is routed to A/D converter 157A and components Pr and Prs areseparately routed to A/D converter 157B. These two converters sample andconvert these three digital signals into three streams (sequences) ofdiscrete digital values, as previously described, reprsentative of thePw, Pr, and Prs signal components respectively. These digital streamsare processed by the computer, in a manner described below, to producetwo concurrent sequences of instantaneous digital sample values. Onesequence represents the simultaneously occurring pressure displacementwaveform variations and the other represents the reference pressure ofthe waveform sensor cuff.

Specifically, the computer generates the pressure displacement waveformsequence by summing each sequential instantaneous corresponding samplevalue of the Pw signal component with its corresponding value of the Prsignal component. Thus, the pressure displacement waveform samplingsequence is comprised of simultaneous heart contraction andrespiratory-induced components, Pw and Pr, respectively. The pressuredisplacement waveform sequence forms the basis of the waveform sensormeasurements produced by routine 630 during the "calibration" phase aswell as for the waveform sensing cuff measurements produced during the"continuous monitoring" phase. Specifically, certain ones of thepressure displacement waveform sample values occurring during the"calibration" phase are used by waveform sensor initialization routine633 (see FIG. 7A) to ascertain the base-level peak and trough values. Inparticular, routine 633 computes base-level peak and base-level troughvalues as the average of the peak amplitudes and trough amplitudesvalues, respectively, of at least one sequence of pressure displacementwaveforms measured at the low constant reference pressure of thewaveform sensing cuff. In the event that the waveform sensing andocclusive cuffs are affixed to different limbs of the subject such as toenable simultaneous sensing therefrom of the same waveform sequence,then this waveform sequence preferably begins with the first waveformdetected as part of systolic determination routine 1020 and ends withthe last waveform sampled as part of diastolic determination routine1030 (both of these routines are shown in FIG. 11 and will be discussedin detail shortly). Alternately, the base-level peak and trough valuescan be computed by averaging the waveform maximums measured duringsystolic routine 1020 and averaging the waveform minimums subsequentlydetected during execution of diastolic routine 1030. In the event thatboth the waveform sensing and occlusive cuffs are affixed to the samelimb, then waveform sensor initialization routine continues to sampleincoming pressure displacement waveform data detected through thewaveform sensing cuff after the occlusive cuff pressure is released andcontinuing for an interval lasting at least as long as 6 heartbeats, ora complete respiratory-induced displacement cycle. The commencement ofthe "continuous monitoring" phase is delayed such that two simultaneoussequences of a suitable number of maximums and minimums can be measuredfrom the waveform sensing cuff to facilitate computation of base-levelpeak and trough values. Once the base-level peak and trough values arecomputed, control proceeds to moduli table determination routine 640which uses these values in fabricating a pressure/displacement look-uptable, as previously described.

As noted, the validity of any displacement waveform sample is alsodependent upon a process of measurement and correction of the referencepressure component in the low pressure waveform sensor cuff. Hence,simultaneous with the computation of the base-level peak and troughvalues during the "calibration" phase, routine 633 also computes abase-level reference pressure. Specifically, the low frequency samplevalue sequence, i.e., the digitized equivalent of the Prs analog signalcomponent, is averaged over one or more preferably completerespiratory-induced arterial displacement cycles, utilizing areasummation or integration and time division methods that are well-knownin the art, such that the base-level reference pressure and its rate ofchange (if any) are determined during the initial "calibration" phaseand first few minutes of the "continuous monitoring" phase. Inasmuch asthe rate of change in the base-level reference pressure reflects anyinitial pneumatic system leakage and/or other system conditions such as,for example, temperature effects on air pressure in the pneumatic systemand/or on pressure transducer operation; the base level referencepressure may not remain constant. Instead this pressure is apt toslightly decrease with time. Since the base-level reference pressurevalue is initially ascertained over a small number (e.g., one or two) ofrespiratory-induced arterial displacement cycles during the"calibration" phase, the "actual" reference pressure values are alsocomputed in like manner throughout the "continuous" monitoring phase.Any differences between the base-level and actual values are used tocorrectively adjust the pressurization of the waveform sensing cuffduring the "continuous" monitoring phase in order to maintain the cuffpressure at the base-level reference value (i.e., approximately 40mm(Hg)). Specifically, the "actual" reference pressure values arecomputed in the same manner as the base-level value. In particular,during the "continuous" monitoring phase, "actual" reference pressurevalues are continuously computed for each adjacent group of, at leasttwo or preferably about three, respiratory-induced arterial pressuredisplacement cycles (of approximately 8-15 pressure waveforms each) soas to update the "actual" reference value every 15 seconds or so.Whenever a pre-defined difference, on the order of one or a few mm(Hg),is determined to exist between the "actual" and the "base-level"reference pressure values, the pressure difference is eliminated throughappropriate corrective inflation or deflation of the waveform sensorcuff. In addition, the rate of change occurring between any twosequential "actual" reference pressure values is computed with respectto the intervening time interval that transpired since the priorcorrection of waveform sensing cuff pressure (or if none occurred sincethe prior calibration, since the determination of the "base-level" valueitself). Each rate of change is subtracted from the "base-level"standard rate of change, and the resulting differential rate of changeis used to determine if the reference pressure change remains relativelystable. If, by contrast, the absolute values of two such sequentiallyoccurring differential rate of change values both exceed a pre-definedlimit, preferably a factor of about -1 of the "base-level" rate (havinga value such as to reflect excessive system leakage), then themonitoring process is terminated and another re-calibration phase isinitiated. In the event that the differential rate of change valuesstill remain excessive, then the pressure in the waveform sensing cuffis vented, an appropriate error message is displayed and the system isshut-down.

2.3.2 Occlusive Cuff Measurements 2.3.2.1 Overview

Essentially at the same time that waveform sensor initialization routine633 is executed, as described above and shown in FIG. 7A, computer 200also executes occlusive cuff measurement routine 636. These two routinesare only executed during the "calibration" phase. Execution of occlusivecuff measurement routine 636 causes the occlusive cuff pressure to bereduced or bled-down, preferably at a linear rate, and the systolic anddiastolic pressure values to be determined based upon simultaneouslyoccurring pressure displacement waveform activity detected throughperturbations in the occlusive cuff pressure.

Occlusive cuff measurement routine 636 is shown in flowchart form inFIG. 11. Upon entry into this routine, control is first passed toocclusive cuff bleed-down routine 1010. This routine initiates andcontrols the linear bleed-down of occlusive cuff by providing, aspreviously described, an appropriate 8-bit bleed-down value, via I/Oport 201 and leads 163, to bleed rate control 144 (see FIG. 1B). Withthe occlusive cuff connected as shown in FIG. 1A, computer 200--throughpneumatic valve 111, pressure transducer 133, signal conditioner 147,A/D converters 157A, 157B, and I/O port 203--obtains a sequence ofdigitized samples of the occlusive cuff pressure occurring during itsbleed-down.

Once an initial number of these samples has been taken and stored in RAMmemory 212 (see FIG. 1B), control passes to systolic determinationroutine 1020, which calculates the systolic pressure based upon largenumber of pressure samples. Specifically, this routine, in a mannerdescribed in detail below, first measures the average time intervaloccurring between the peaks of detected pressure displacement waveformsto determine the existence of any "absent" pulse intervals or "windows".Since the force imparted by pulsatile arterial blood pressure waveformscan and, in fact, does normally vary from heart-beat to heart-beat, someresulting displacement waveforms occur with a greater intensity(amplitude) than others. As a result, some of these resulting waveformsmay occur with an amplitude (force) that is too small to impart anymeasureable variations to the pressure of the occlusive cuff during theearly relatively high-pressure part of the bleed-down process. Thesewaveforms are thus commonly referred to as being "absent" during apre-determined or calculated sampling interval or "window" Absent pulsewindows (APWs) may also be illustratively caused by an irregularheart-beat which generates non-uniformly spaced pressure displacementwaveforms. The resulting number and relative position (in the waveformsequence) of such APWs that may be identified determines, in part, whichspecific method will be used for measuring the systolic pressure.Specifically, the systolic determination routine 1020 selects, largelybased upon this APW information, one of four methods which are describedin much greater detail below.

Once the systolic measurement has been determined, control is passed todiastolic determination routine 1030 which primarily consists of twoseparate but essentially simultaneously executed processes, namely meanprofile routine 1033 and sliding slope routine 1037, that processadditional pressure displacement waveform sample data to generate twoseparate diastolic pressure values, DPmp and DPss, respectively.Validation routine 1040, in a manner to be described shortly, comparesthese two diastolic pressure values and, based upon the magnitude of anydifference therebetween and on the type of variability encountered ineach of the two processes, selects one of these two values, and, ifnecessary, modifies it to produce a final diastolic pressuremeasurement. If, by contrast, validation routine 1040 cannot make such aselection, due to excessive variability in the sampled pressure waveformdata, then this routine re-inflates the occlusive cuff, via occlusivecuff inflation routine 770, to repeat all the occlusive cuffmeasurements.

Once validation routine 1040 produces a diastolic pressure measurement,the occlusive cuff is completely deflated at a fast pre-defined rate byexecution of routine 1050, and thereafter control exits from occlusivecuff measurement routine 636 and transfers to moduli table determinationroutine 640.

2.3.2.2 Systolic Measurement

To enhance understanding the operation of systolic occlusive cuffmeasurement routine 1020 (referred to in FIG. 11), and shown in detailin flowchart form in FIGS. 12A-12G, the readers attention is firstdirected to FIGS. 15A-D, 16A-H and 17A-H which graphically show theoperation of this routine for various illustrative sequences of PWA(pressure waveform amplitude) peaks.

FIGS. 15A-D illustratively show four separate cardiovascular hemodynamicsequences of arterial blood pressure waveform amplitude (PWA) valuesoccurring during the bleed-down of an occlusive cuff. Althoughindividual blood pressure waveforms are of the form shown in FIG. 6, forpurposes of clarity, only the peak amplitude of each pressure waveformis shown as a vertical line in FIGS. 15A-D. Hence, each line signifiesthe occurrence of one pressure waveform during a cuff measurementsequence of several waveforms. The four sequences reflect hemodynamicconditions of increasingly variable nature, depicted in such a manner asto be taken as representative of a broad range of cardiovascularactivity that can be encountered in practice.

Superimposed upon each pressure waveform amplitude sequence in FIGS.15A-D is one or more generally descending dashed lines, each of whichdepicts the decreasing pressure of an occlusive cuff. Each dashed lineis an illustrative example of a separate occlusive cuff bleed-down thatcould occur during the systolic measurement routine. As shown, thepressure in an occlusive cuff is bled-down at an approximately linearrate which is always interrupted by a constant pressure samplinginterval that is depicted by a horizontal dashed line segment. Thelocation of the alternate dashed lines of FIGS. 15C and 15D differ fromeach other in that the position of each line is dependent upon the timeat which occlusive cuff pressure bleed-down process is initiatedrelative to the particular waveform sequence. Since initiation times arerandom in nature, initiation time is often a factor which influences themeasurement results of any occlusive cuff process known in the art,particularly when substantial hemodynamic variability is present.

Whenever any blood pressure waveform sufficiently distends an arterialwall to produce a force which generates a pressure onto the occlusivecuff in excess of the simultaneously occurring occlusive cuff pressurerepresented by the dashed line, that force increases the pressure of theair contained within (internal to) the occlusive cuff. This increasegenerates a pressure pulse, i.e. a so-called pressure displacementwaveform, which varies the air pressure in the occlusive cuff and is, inturn, sensed by control and measurement unit 100. Conversely, wheneverany blood pressure waveform results in a force that produces a pressureonto the occlusive cuff which is equal to, or less than, the internalocclusive cuff pressure, then no pressure variations are imparted to theocclusive cuff pressure. In this case, a pressure displacement waveformis not detected. The sampling interval of these latter undetectedwaveforms are the previously described APWs (absent pulse windows).FIGS. 16A-H graphically show sequences of detected relative pressuredisplacement waveform amplitudes (PWAs)--i.e. amplitudes in excess ofthe descending occlusive cuff pressure--that illustratively are detectedusing an occlusive cuff for each of the dashed line bleed-down sequencesshown in FIGS. 15A-D.

Systolic determination routine 1020 produces through occlusive cuffmeasurements a final value of systolic pressure, SP, and this routinepossesses specific measurement attributes which advantageously enhances"continuous monitoring." In this regard, the primary attribute ofsystolic routine 1020 is its ability to compensate forheartbeat-to-heartbeat hemodynamic variability and bleed-downinitialization random errors (due to the occlusive cuff pressure notbeing equal to the initially-detected pressure waveform peak pressure)that are a source of measurement unreliability with occlusive cufftechniques known in the art. Essentially, this routine consists ofsampling for a sequence of typically 4-6 pressure displacement waveformsduring the initial phase of the occlusive cuff bleed-down process(during the period when the occlusive cuff pressure is initiallydecreasing and then remaining constant) followed by an interpolativeweighting process performed in a manner which approximates themeasurement accuracy of calibrated blood pressure waveform averagingcomputations of direct invasive monitors. This interpolative weightingprocess makes use of the ascent rate during bleed-down sampling, as wellas the variability during constant pressure sampling (CPS), of all PWAsdetected in same sampling intervals to yield a tentative systolicpressure value, sp. Based on the type and relative amounts ofhemodynamic variability, if any, exhibited in the detected waveformsequence, other compensatory methods, as will be described in detailshortly, are executed to modify, if necessary, the tentative systolicpressure in order to determine the final systolic pressure value, SP.Specifically, the interpolative process consists of determining theco-ordinate pairs of two points "A" (anchor) and "P" (pivot), based uponthe amplitude value and time of occurrence (in terms of the thenoccurring occlusive cuff-pressure) of detected PWAs, as well as thenumber and relative location of any ascertained APW's, for any plausiblepattern of hemodynamic variability. These two points "A" and "P" definethe path of a straight line (hereinafter referred to by the term"vector") that is passed through both points. This "vector" is thenlinearly extended backward to the 70-axis from point "P" to a tentativevalue of systolic pressure, sp, that is determined by the x-interceptvalue. Thereafter, the final systolic pressure value, SP, is taken to beeither the value of sp itself or this value modified by a calculatedamount which compensates for specific types of hemodynamic variabilityindicated by the detected PWA sequence.

With the foregoing in mind, an explanation will now be presented of theflowchart of systolic determination routine 1020, shown in FIGS.12A-12G.

After bleed-down of the occlusive cuff has been initiated and the firstpressure displacement waveform peak has been detected by routine 1010(see FIG. 11), control is first passed to block 1101 within systolicdetermination routine 1020 shown in FIG. 12A. This block determines thevalues of the first two PWA peaks, PWA1 and PWA2, occurring duringbleed-down along with the simultaneously occurring occlusive cuffpressures OCP₁ and OCP₂, and executes pulse window interrogation (PWI)routine 1250 to determine the number of any APW's occurring betweenthese peaks. Routine 1250, in a manner which is described in detaillater, establishes the duration of a PWA peak sampling "window," basedupon either certain pre-established standard PWA interval values or theactual duration between earlier-occurring PWA peaks through which theoccurrence of a prior APW has been ascertained.

On completion of block 1101 and measurement of PWA1 and PWA2, controltransfers to execution block 1109 which terminates occlusive cuffpressure bleed-down and maintains the occlusive cuff pressure at aconstant value, OCP_(c), which is the x coordinate of anchor point "A"and which preferably occurs between the value of PWA2 and the value ofthe next subsequentially occurring PWA peak, PWA3.

Thereafter, block 1113 measures the third and fourth PWA peaks, i.e.PWA3 and PWA4, occurring at constant cuff pressure OCP_(c) and, throughthe continued execution of PWI routine 1250, updates the identificationof, and the number of, any APW's intervening between peaks PWA3 andPWA4. During this APW updating process, the duration of the PWA samplingwindow is adjusted based upon the actual time of occurrence of priorPWAs, e.g. PWA3 and PWA4. Once all these PWA peaks and interveningAPW's, if any, have been detected, decision block 1114 determines thevariability of the resulting sequence of PWA peaks, i.e. PWA1, . . . ,PWA4. In the event the measured PWA-to-PWA variability is low--i.e. thevalues of these peaks satisfy certain empirically defined mathematicalcriteria defined in block 1114, then the systolic pressure can bereadily determined--based on a minimum number of 4 PWAs and the shortestsampling duration possible at the constant cuff pressure OCPc. Inparticular, if first, no APW's have occurred prior to PWA4, and second,the ascending values of peaks PWA1 and PWA2 lie between certainpre-defined empirical ranges as determined by various inequalities indecision block 1114, and third, the values of PWA3 and PWA4 are eachwithin 15% of the minimum of PWA3 and PWA4, then control passes to block1115, in FIG. 12B, via the "yes" path from decision block 1114.

Block 1115, when executed, determines the co-ordinates (x_(p), y_(p)) ofpivot point "P". Specifically, x_(p) is the average value of theocclusive cuff pressure values, OCP₁ and OCP₂, which existed at the timeof occurrence of peaks PWA1 and PWA2, respectively, and y_(p) is theaverage value of the peak values PWA1, and PWA2. Once the "P"co-ordinates are determined, block 1117 then computes the y coordinateof anchor point "A" as the average value of all PWA peaks that occurduring the constant pressure sampling interval, henceforth referred toas PWX. The x co-ordinate of point A is taken to be the pressure of tneocclusive cuff during the constant pressure sample interval, i.e.OCP_(c) Thereafter, control passes to block 1116 which executes systolicpressure intercept calculation routine 1300 shown in FIG. 14, whichconnects the co-ordinates of anchor point "A" and pivot point "P" tocreate the vector which is then extended downward to the x-axis, i.e.,to an intercept point. In particular, upon entry into this routine,block 1305 calculates the slope, m, of the vector which passes throughpoints "A" and "P." The value of slope m is then used in execution block1310 to calculate the x-intercept, i.e. the intermediate systolicpressure value, sp, of this vector.

Alternatively, if signal noise or other similar adverse affectsconstantly occur, the intermediate systolic pressure, sp, can be takenas the x co-ordinate of the point of intersection of the downwardlyextended vector with a slightly raised horizontal line (e.g. wherey=0.5) in order to compensate the systolic pressure for these factors.Once the intermediate systolic pressure is obtained, control is thentransferred via block 1118 to block 1220 (in FIG. 12G) which assignsthis intermediate systolic pressure as the final value of systolicpressure, SP, and thereafter control exits from systolic determinationroutine 1020 to diastolic routine 1030.

Alternatively, in the event that decision block 1114 determines that thevariability between the detected PWA peaks exceeds the specified ranges,control is transferred, via its "No" path to block 1119. This latterdecision block tests for an aberrant value of PWA1, i.e. a value whichexceeds the value of PWA2 by more than approximately 25% of PWA2. Shouldthis occur, then the PWA1 value is set equal to the 1.25 times the PWA2value. Control is thereafter passed to block 1121 which extends theduration of constant pressure sampling for the measurement of additionalPWAs. Specifically, sampling at the constant pressure OCP_(c)--henceforth referred to as constant pressure sampling or "CPS"--iscontinued for a finite number of PWA sampling windows, based on the APWoccurrences that are determined by execution of PWI routine 1250, untilone of the following conditions occurs: (a) four adjacent PWAs (i.e.PWA3, . . . , PWA6) with no intervening APW's are detected during fouradjacent constant pressure sampling windows, (b) a minimum of three PWAs(i.e. PWA3, PWA4, PWA5) and one or two intervening APW's are detectedduring a total of 5 adjacent pulse window sampling, intervals, orlastly, (c) five such PWAs with up to three intervening APW's aredetected during a maximum of 8 sequential pulse sampling windows. ThesePWA amplitude values, the corresponding cuff pressure at which eachoccurs, and the number and relative location of all intervening APW'sare all appropriately stored in RAM memory within computer 200 as theyare detected.

Control is thereafter transferred to decision block 1123--shown in FIG.12C--which tests for the occurrence of an undesirable PWA sequence,namely those otner than that defined in block 1121 or in block 1281 ofPWI routine 1250 (which is described in detail later in conjunction withFIGS. 13A-B). If such an undesireable sequence occurs, control thenpasses to block 1124 which terminates the occlusive cuff measurementprocess, dumps the pressure in the occlusive cuff and proceeds toroutine 620 to completely repeat the occlusive cuff measurements.Alternatively, if the PWA sequence can furnish the basis of an accuratesystolic measurement, then control transfers via the "no" path ofdecision block 1123, to execution block 1129. This latter blockcalculates the co-ordinates (OCP_(c), PWX) of anchor point "A" where PWXis the average value of all the sampled PWA peaks occurring after PWA2(i.e. PWA3, PWA4, . . . , PWAn) which were sampled pursuant to block1121, and OCP_(c) is the constant pressure at which the occlusive cuffis maintained after the second pressure waveform peak PWA2. Thereafter,co-ordinate determination routine 1141 computes the co-ordinates ofpivot point "P" (x_(p), y_(p)) using formulas that differ based on thenumber of intervening absent pulse windows, (either confirmed APWs, ortentatively identified APW's hereinafter referred to as TAPWs) thatoccured between PWA1 and PWA2. Specifically, when no APWs are identifiedto have occurred between PWA1 and PWA2, which is the most typicallyencountered hemodynamic condition and is shown in FIG. 16A, then x_(p)is taken to be the average of cuff pressures, OCP₁, and OCP₂, thatexisted at the time PWA1 and PWA2 occurred, and y_(p) is taken to be theaverage of the values of PWA1 and PWA2. However, if one such APWoccurred therebetween, then xp is instead taken to be equal to apressure value greater than OCP₂ by an amount equal to one-half of theamount of pressure reduction, (i.e., OCP_(API)) that occurred during theprevious sampling window based on ongoing pulse interval calculationsthat are performed in PWI routine 1250 (to be described later).Furthermore, if two such APWs are determined by PWI routine 1250 to haveoccurred, then the y_(p) computation is also altered, such that y_(p) isset equal to the value of PWA1 plus one-fourth of the difference betweenPWA1 and PWA2. Control then proceeds from block 1141 to block 1145--seeFIG. 12D--which executes systolic pressure intercept calculation routine1300 to find the above described x-intercept value that defines theintermediate systolic pressure value, sp.

Once this intermediate value has been determined, decision block 1168then tests for a particular type of hemodynamic variability whichrequires additional PWA sampling and measurement computations.Specifically, whenever APWs occur after, but not before, PWA2, controlis transferred to execution block 1169 (shown in FIG. 12E) via the "yes"path from block 1168. Execution of block 1169 causes a second samplinginterval to occur during which the air pressure in the occlusive cuff isfirst reduced by a pre-defined amount, preferably about 10 mm(Hg), andthereafter the pressure is then maintained constant at the valueOCP_(2c) for a second constant pressure sampling (CPS) interval. Duringthis second CPS interval, block 1173 executes PWI routine 1250 whichsamples the occlusive cuff pressure for a pre-selected number ofadditional sampling windows. This number is dependent upon the number ofpreviously identified APW's occurring during the first CPS interval.Specifically, if one, two or three APW's were previously detected, thensampling continues for six, seven or eight sampling windows during thesecond CPS interval, respectively. The amplitudes for this secondsequence of measured pressure displacement waveforms (denoted as, PWA₂₁,PWA₂₂ , . . . , PWA_(2n)), as well as the relative position and numberof intervening APW's, if any, occurring during the sampling windows ofthe second CPS interval are stored in RAM 212 (see FIG. 1B) forsubsequent processing.

Thereafter as shown in FIG. 12E, decision block 1177 tests for the rateof occurrence of APWs in the second CPS interval at OCP_(2c).Specifically, when two or more APWs are identified to have occurredafter the first PWA is measured in any subsequent CPS, that CPS interval(denoted as PWAx interval) is terminated and execution blocks 1169 and1173, as described above, are repeated once, as directed by execution ofdecision block 1178 and block 1180, such that a third CPS interval isconducted at OCP_(3c). If the APW test of decision block 1177 failsagain at OCP_(3c), i.e. during this third CPS interval, control istransferred from block decision 1178, via its "yes" path, to block 1181.When executed, this latter block terminates the occlusive cuffmeasurement process, dumps the occlusive cuff pressure and repeats theocclusive cuff measurement process by transferring control to routine620. If re-execution of the occlusive cuff measurement process fails toproduce a PWA sequence that satisfies the test in decision block 1177,then block 1181 terminates all the occlusive cuff measurements, dumpsthe air pressure in both cuffs and displays an appropriate errormessage. System shutdown follows thereafter.

Alternatively, if the number of detected APW's is sufficiently small(e.g. one) during either the second or third CPS, block 1177 transferscontrol, via its "no" path to decision block 1182 which sets a limit onthe value of intermediate systolic pressure sp determined pursuant tothe execution of routine 1300 as previously envoked by block 1145. Thislimit on the intercept calculation effectively prevents unlikely butpossible artifact occurences from causing a substantially erroneousfinal systolic pressure measurement. Specifically, in the event that thex-intercept sp value previously determined in routine 1300 exceeds aspecified occlusive cuff pressure, OCPs, control is transferred fromblock 1182 via its "yes" path to execution block 1183 and the specifiedOCP (i.e. OCPs), becomes the value of sp instead of the value determinedby routine 1300. In block 1182, the specified pressure value, OCPs isinterpolated from previously recorded actual linear bleed-down data tobe the cuff pressure that existed prior to PWA1 by the equivalentbleed-down amount of three sampling windows where the duration of onesuch window is determined by PWI routine 1250 as the average ofpreviously measured heart-rate intervals.

After the sp value has been redefined if necessary, control is thentransferred from block 1183, or via the "no" path from block 1182 toblock 1185--shown in FIG. 12F. Block 1185 first finds the three largestPWA peak values occurring during the most recent CPS interval (e.g.,PWA_(2x), PWA_(2y), P_(2z), assuming the second CPS interval was themost recent) and calculates their average value PWY_(p). Thereafter,this block also calculates the average value PWY, of all the detectedPWA peaks occurring during tne most recent sampling interval (e.g.,PWA₂₁, PWA₂₂, . . . , PWA_(2n), again assuming the second CPS intervalis the most recent). Lastly, this block determines the differentialocclusive cuff pressure, OCP, which is the total change in occlusivecuff pressure from that of the original CPS to the pressure of the mostrecent CPS interval (e.g. OCP_(c) -OCP_(2c) or alternately OCP_(c)-OCP_(3c) if the third is the most recent). Once these operations arecomplete, execution block 1187 calculates final systolic pressure SP bymodifying the intermediate systolic pressure value, sp, based upon thedifferential occlusive cuff pressure OCP, and the calculated averagevalues PWY, PWX and PWY_(p).

After the final systolic pressure value, SP, is calculated, control thenproceeds to decision block 1188 which tests the difference between theintermediate and final systolic pressures, sp and SP, to determine ifits downward adjustment exceeds a pre-determined maximum of 6 mm(Hg) foreach APW that occurred in the first four sampling windows of the mostrecent CPS interval. In the event this difference is excessive, thencontrol proceeds to execution block 1189 which increases SP by theamount which the difference, sp-SP, exceeds the predetermined maximumdownward adjustment. The resulting SP value produced by block 1189 isthe final systolic pressure measurement. As a result, control exits fromblock 1189 and thus from systolic routine 1020 and proceeds to diastolicroutine 1030.

When the result of the tests in previously described decision block1168--see FIG. 12C--is "no", this indicates the existence of absentpulse windows (TAPW or APWs) occurring between PWA1 and PWA2 andpossibly during the initial CPS interval occurring after PWA2, or thatno APW's have occurred after PWA1 until after the completion of theinitial CPS interval. Consequently, execution proceeds through up tothree additional decision blocks to set maximum limits on theintermediate sp value. These blocks, 1190, 1192 and 1194, test for theexistence of 0, 1, or 2 APW(s), respectively, and whichever one of theseconditions occurs first, precludes the execution of the remainingdecision blocks. In the event 0, 1 or 2 APWs have occurred, blocks 1191,1193 or 1195, respectively, are executed. These blocks set a limitingvalue on the intermediate systolic pressure value, sp, determined byroutine 1300 through execution of block 1145. The purpose of theselimits is to prevent unlikely but possible, aberrant results fromproducing an erroneous final systolic pressure measurement. In each ofblocks 1191, 1193, and 1195 the previously determined intermediatesystolic pressure value, sp, is compared with a respective one of threeempirically pre-determined OCP values, OCP_(E1), OCP_(E2), OCP_(E3), andif the value sp exceeds its respective OCP_(E) value, then this OCP_(E)value becomes the value of sp instead of that determined throughsystolic intercept routine 1300. These pre-determined OCP_(E) values(OCP_(E1), OCP_(E2) and OCP_(E3)) are the interpolated cuff pressuresthat existed during the bleed-down one and one-half or one pulse windowinterval prior to the occurrence of PWA1 for execution of blocks 1191and 1193, respectively, and one and one-half pulse window intervalequivalents prior to the occurrence of PWA2 for execution of block 1195.

If either block 1193 or 1195 is executed, then control thereaftertransfers to block 1220 which assigns the previously determinedintermediate sp value, as adjusted, to be the final systolic pressuremeasurement, SP. This ends the execution of systolic determinationroutine 1020 and control is transferred to diastolic determinationroutine 1030.

Alternatively, if block 1191 is executed, control is transferred toblock 1199 which is shown in FIG. 12G and described in the followingparagraph. Alternately, in the event that control is transferred via the"no" paths of blocks 1190, 1192 and 1194, then this indicates that threeor more APWs exist between PWA1 and PWA2. As a result, control istransferred to execution block 1281 of pulse window interrogation (PWI)routine 1250 which erases the previously-stored value for PWA1. The nextsuccessive PWA value after the PWA1 is then identified to be PWA1, andthe OCP bleed-down is then continued until immediately after a third PWApeak (including the erased PWA1) is detected. The third PWA peak isidentified as PWA2 and the bleed-down is terminated for the initial CPSinterval. Block 1281 then appropriately routes execution to complete theremainder of systolic pressure determination routine.

Decision block 1199 is executed, whenever control is transferred fromexecution block 1191 to determine whether any intervening APWs haveoccurred prior to CPS thereby indicating a relatively significant amountof hemodynamic variability. Specifically, this decision block identifiesany pressure displacement waveform sequence in which no APWs haveoccurred after PWA2 and where the hemodynamic variability of peak valuesPWA3 through PWA6 (as compared to their average, PWX) is significantlyless than the level of variability exhibited between detected PWA1 andPWA2. As the reader will recall, the pivot point "P" coordinates (xp,yp), as computed in block 1141, are based in part on the premise thatthroughout the CPS interval, the amount of PWA-to-PWA variability,between PWA1 and PWA2, can be specified by the actual number of APWsencountered and the bleed-down rate. Hence, block 1199 identifies thosesequences where the variability exhibited during the CPS interval issignificantly less than during the PWA1-PWA2 interval. Thus, if all theconditions specified in decision block 1199 are true for a particularPWA sequence, then execution proceeds down the "Yes" path to decisionblock 1203. There, based upon whether one or two APW's have occurredprior to the occurrence of pressure waveform peak PWA2 (and nonethereafter), such as, for example, as shown in FIGS. 16C, D, E and G, aconstant, K, is set to an appropriate value. This value is used in theformula specified in execution block 1215 to modify the intermediatesystolic pressure, sp, to yield the final systolic pressure value, SP.At the conclusion of block 1215, execution then exits from systolicdetermination routine 1020 to Diastolic Determination Routine 1030.

Alternately, if the exhibited PWA variability is generally consistentfrom PWA1 until the end of the CPS interval, then execution proceedsalong the "no" path from block 1199 to block 1220 which then assigns theintermediate systolic pressure value, sp, to be the final systolicpressure measurement, SP. Thereafter, execution proceeds from systolicdetermination routine 1020 to diastolic determination routine 1030.

The pulse window interrogation (PWI) routine 1250 as previouslydiscussed, is shown in flowchart form in FIGS. 13A-B. Entry into thisroutine occurs at block 1251, which is executed essentiallysimultaneously with the detection of PWA1 in block 1101 of systolicdetermination routine 1020. Thereafter control immediately proceeds toexecution block 1263 wherein, after each PWA is detected (beginning withPWA1), a sampling window of a pre-defined duration is "opened" duringwhich either a PWA, APW, or TAPW (tentative identification of an APW,i.e. an identification of an APW which is to be confirmed at a laterprocessing step) is to be detected. After sampling occurs for thisduration, control proceeds to execution block 1265 which records thetype and time of occurrence of the intervening detected APW, if any, andupdates the previously stored PWA peak sequence data based oncomputations performed in execution blocks 1271 and 1273, both of whichare described shortly. The duration of each new sampling window is basedon available pre-determined standard or updated actual heart-rateinterval averages that are maintained in memory and made availablethrough execution of block 261. In particular, as many as three types ofthese averages can be resident in the memory, and one is initiallyselected in order to set realistic durations for each successive newsampling window. Specifically, a standard window, SW1, of approximately1.4 seconds, is used to establish the duration of the successivesampling window which begins at the time the peak of the most recentlydetected PWA peak, i.e. PWA_(n), occurs--assuming this peak occurredduring the most recent sampling window. However, if the most recentlydetected sampling event was a TAPW or APW, then a standard window, SW₂,of approximately 1.1 seconds in duration is used and this durationbegins at the end of the prior SW1 interval. Alternatively, instead ofusing any such pre-determined window values, the "a posteriori" windowvalue, specifically the average pulse interval window (APIW), ifavailable, can be used. The APIW duration is calculated, by executionblock 1272, by multiplying the duration of most recent average pulseinterval (API) value, which is described next by a factor ofapproximately 1.2. The most recent API, which is a "running" average ofall prior actual heart-rate intervals detected during systolic routine1020, is computed by block 1271 after each additional peak, PWA_(n),value is detected. However, prior to the execution of block 1271 foreach newly detected PWA_(n) value, decision block 1269 is executed todetermine whether an intervening APW (occurring between PWA_(n) andPWA_(n-1)) has occurred.

In the event a peak value, PWA_(n), occurs during the most recentsampling window and no APW's intervene between peaks PWA_(n) andPWa_(n-1), then decision block 1269 routes control to block 1271 whichinitially computes and thereafter updates the APIW value. If the totalnumber of these sampling windows is greater than unity (i.e. two ormore), then control proceeds from block 1271 to execution block 1272.This latter block computes the duration of above-defined APIW for use inestablishing the duration of subsequent sampling windows instead ofusing any standard window (SW) value. With each iterative APIcomputation performed by execution block 1271 when "m" is greater thanunity, control also proceeds to execution block 1273 which recomputesall TAPW and APW window intervals, beginning with the occurrence ofPWA1, based on the latest computed API value. All the computed windowintervals are substituted for the previously calculated windows. Oneresult of these computations, for example, is the redesignation of anytentative absent pulse windows (TAPWs) to being APWs (when extremevalues of API are computed in practice, it is possible that more thanone APWs can be redesignated by this block). Another result of executingblock 1273 is that the APW occurrence data is updated for use in block1267. The particular sampling window occupied by an APW in any samplingsequence is identified by the subscript p as shown in block 1263.

During any "re-calibration" of the occlusive cuff (i.e., after priorcontinuous monitoring data has been acquired), an MAPIW value (describedbelow), as computed in block 1261, can preferably be used in place ofeither SW durations when the value of "m" is one or less, or the currentAPI value when the value of "m" is two or three. Specifically, executionblock 1261 computes an average pulse interval window, for the MAPIWvalue, which is the product of a constant, approximately 1.2, and thereciprocal of the average heart-rate (1/HR). The heart-rate measure iscomputed from sequential pressure waveform data measured during the mostrecent measure of continuous monitoring.

At the conclusion of each sampling window, during which, as noted, APWsare detected and PWA sequences are defined, control proceeds from block1265 to decision block 1267. If an APW has been identified in the latestwindow or a redesignated change to APW status has occurred, then controlproceeds via its "no" path to decision block 1275, as it does fromdecision block 1269. Decision block 1275 tests for all possiblesequences in which three APWs (and TAPW's) can occur, particularly withrespect to interval between PWA1 and PWA2 and that between PWA2 andPWA3. In the event such a sequence occurs, then control proceeds toexecution block 1281 which removes PWA1 from the sequence and relabelsthe remaining PWA peaks such that PWA2 becomes PWA1. Any interveningAPWs prior to the new PWA1 are disregarded. Thereafter, bleed-down iscontinued until a new PWA2 is detected. Otherwise, if the bleed-down hasalready been terminated and CPS has commenced by the time block 1281 isexecuted, then all window data acquired during the CPS interval iserased from memory. For this case, bleed-down is then resumed until anew PWA2 is detected before the CPS phase can be re-entered, at whichtime both systolic routine 1020 and PWI routine 1250 are re-initialized.Otherwise, in the absence of a "yes" condition in block 1275, controlproceeds via its "no" path to decision block 1277. This latter decisionblock ascertains whether window sampling should continue based on thepre-designated CPS sequences defined in other blocks of systolic routine1020. If any of these sequences has not yet occurred, then controlproceeds via the "no" path from decision block 1277 to block 1279 whichopens the next sampling window. Otherwise control exits from block 1277and PWI routine 1250, and at the completion of systolic determinationroutine 1020 control proceeds to diastolic determination routine 1030.

2.3.2.3 Diastolic Pressure Determination

Once the final systolic pressure value, SP, has been determined,diastolic determination routine 1030 is executed to determine twointermediate diastolic pressure values, DPmp and DPss. DPmp isascertained via mean profile routine 1033 and DPss is ascertained fromsliding slope routine 1037. Thereafter, diastolic validation routine1040 selects one of these two intermediate diastolic pressure values,modifies it if necessary, and then sets the final diastolic pressuremeasurement equal to the result. Once this routine completes itsexecution the occlusive cuff measurement processes of the "calibration"phase are completed.

2.3.2.3.1 Mean Profile Routine 1033

Mean profile routine 1033, is shown in flowchart form in FIGS. 18A-B.However, to facilitate understanding of the basis of this routine,discussion will first center on FIG. 19A which shows a sketch of asingle typical pressure waveform. During any occlusive cuff bleed-downprocess of pressure sensing methods known in the art, the peak amplitudevalues of all detected pressure displacement waveforms exhibit theapproximate characteristics of a curve, or envelope, as shown in FIG.19B.

Pressure sensing systems known to the art measure diastolic pressurethrough methods based on an assumed static linear relationship betweenmean and diastolic pressures. It is known from empirical studies in theart tnat mean pressure M is generally equal to the value of theocclusive cuff pressure (OCP) during the largest pressure displacementwaveform amplitude in the envelope (i.e. PWA_(peak)). Given this, theseprior art methods employ what is often termed a "threshold" mechanism,which is premised on maintaining a proportional relationship betweendisplacement waveform amplitudes at the mean and diastolic occlusivecuff pressures. Specifically, as the occlusive cuff pressure is reduced,and mean pressure (the "threshold") is determined, the linearrelationship is extrapolated downward to define a suitable diastolicpressure. Unfortunately, these prior art threshold methods implicitlyassume a fixed linear arterial elasticity relationship for all of thehuman population --which in fact is not the case, and thus use a methodin which diastolic pressure measurements are inherently anddisadvantageously biased to be primarily dependent on mean pressurephysiologic parameters instead of parameters that are directly relatedto diastolic pressure. Thus the prior art methods for determiningdiastolic pressure generally yield inconsistent results.

The inventive diastolic mean profile method solves for a specificdiastolic pressure value that can be derived from any and all of severalindividual pressure displacement waveforms during the latter phase ofthe descent of occlusive cuff pressure. Such individual measurementvalues depend on the values of certain waveform profile parameters thatare directly related to each diastolic pressure value, namely theamplitude and integrated area of each individual pressure displacementwaveform. In addition, the embodied method, preferably, but notnecessarily, includes the attribute of averaging the results of severalof such individual waveform measurements, e.g., approximately four tosix in number, before a final weighted value is computed, in much thesame manner as is done by direct invasive monitors. The inventive methodis executed after the systolic and mean pressures have been determinedso that the waveform parameter measurements can be taken when theocclusive cuff pressure is relatively low in order to minimize waveformdistortion, if any, that usually results from relatively high appliedcuff pressures. Specifically, as the applied occlusive cuff pressure isreduced from systolic and approaches the diastolic pressure, the amountof externally induced impedance and reflectance that tends to alter thefrequency characteristics and relative shape of any pressuredisplacement waveform diminishes. This distortion gradually disappearswith the latter-stage waveforms that occur after PWA_(peak), and becomesessentially nonexistent when the occlusive cuff pressure becomesapproximately equal to, or less than, the diastolic pressure.

The diastolic pressure of any such latter-stage pressure displacementwaveform, one of which, for example, is illustratively shown in FIG.19A, can be determined from the following relationships: ##EQU1## Aftersubstituting the expression for x given by equation (1) into equation(2) and simplification, the following equation results:

    D=AM-Sy/(A-y)

where A is the uncalibrated amplitude of any latter-stage pressuredisplacement waveform, y is the uncalibrated mean value (area/duration)of the waveform, and S, M, and D are the patient's systolic, mean, anddiastolic blood pressures, respectively.

The initial phase of the mean profile method is comprised of continuallytesting groups of pressure displacement waveform amplitudes duringocclusive cuff bleed-down in order to determine the largest waveformamplitude value and a corresponding occlusive cuff pressure (OCP) value,M. The next phase involves averaging a pre-defined sequence ofindividual waveform diastolic values to yield a diastolic pressuremeasurement. In this latter process, individual measurements ofuncalibrated waveform values, A and y, are successively substituted intoequation (2) above along with previously determined values of S and M,and the equation is solved for the only unknown variable term, d(i) forthe diastolic pressure value associated with each particular waveform.

Now, upon entering mean profile routine 1033, as shown in FIG. 18A,blocks 1805 through 1815 are executed to find the group of PWA values(illustratively and preferably four in number) that possesses thelargest average value. Specifically, block 1805 sets up a runningaverage, R₁ for the first four PWAs (PWA1, . . . , PWA4) which have beendetected during the previously-executed systolic determination routine.Thereafter, block 1810 deletes the "oldest" PWA peak value (e.g., PWA1),replaces it with the next PWA peak value (e.g., PWA5) and thenrecomputes the average of the four peaks as R₂. If the average valueincreases, i.e., the value of R₂ is larger than that of R₁, therebysignifying that these four most recent peaks preceed the occurrence ofthe maximum peak and are thus on the ascending portion of the envelope,then decision block 1815 causes block 1810 to transfer execution, viathe "Yes" path, to execution block 1813. This latter block assigns valueR₂ to value R₁ and also stores the numbers (index values) associatedwith each of these four peaks for use in subsequent identification andretrieval of these peaks. As long as the average value continues toincrease, decision block 1815 re-executes blocks 1813 and 1810 to findthe four largest peaks. However, once the average value begins todecrease and continues decreasing execution proceeds, down the "No" pathfrom decision block 1815, to block 1820. Execution block 1820 firstaccesses the four PWA values from which the maximum average value wascalculated, and then determines the largest PWA value (PWA_(peak)) fromamong these four peaks. However, for purposes of insuring that artifactsdid not cause PWA_(peak) to occur, the selection of PWA_(peak) issubject to the criteria that the PW_(peak) value cannot exceed the valueof the next largest detected PWA by more than 20%. If the value ofPWA_(peak) exceeds this 20% limitation, then this peak value isdiscarded from the analysis and the next largest peak value is selectedfor PWA_(peak) and the selection criteria is applied to this new value.This selection process continues until a PWA_(peak) value is producedwhich satisfies the criteria. Mean pressure M is then determined to bethe occlusive cuff pressure that existed at the time of occurrence ofthe PWA_(peak) that is finally selected.

The remaining blocks, shown in FIG. 18B complete the mean profilemeasurement of diastolic pressure, DP_(mp). Specifically, block 1870recognizes and enters each pressure displacement waveform occurringafter PWA_(peak) into an iterative process in which individual diastolicpressure measurements d(i) are determined from each successive pressuredisplacement waveform pursuant to execution block 1871. In particular,this block first calculates the area, a(i), under each such uncalibratedwaveform, PW(i), by integrating the difference between all of thewaveform sample values and the simultaneously measured linearly varyingocclusive cuff pressure values. Thereafter, an uncalibrated meanpressure value, y(i), is calculated for each waveform by dividing areaa(i) by its period (duration) t(i). A diastolic pressure value, d(i), isthen determined for each waveform, PW(i), pursuant to step 3 in theblock 1871 where: A(i) is the uncalibrated amplitude of waveform PW(i);M is the occlusive cuff pressure occurring at PWA_(peak) (determined byblock 1820); y(i) is the uncalibrated individual mean pressure of PW(i);and S is the systolic pressure SP determined in routine 1020.

In addition, blocks 1872 and 1874 through 1876 are used to eliminatedivergent d(i) values that might occur due to artifacts. Specifically,when three d(i) values are computed, block 1874 begins to check fordisparate values that vary by more than approximately 15% of eachaverage that can be computed from all possible paired combinations ofdiastolic values. Any such disparate value is eliminated from furthercalculations in block 1874 and the indexing system (i) is appropriatelyadjusted in block 1876. In addition, when (i) exceeds 2, block 1874compares each new d(i) value to the average of all prior acceptabled(i-1) values, rejecting any additional values as being disparate basedupon the 15% difference. Block 1877 computes a running average of theacceptable d(i) values, D_(n), for the next comparison. Execution blocks1880 through 1883 determine the point when the occlusive cuff pressureconverges to become equal to the continually updated average, D_(n). Atthis point, a latter-stage waveform sequence can be identified such thatthe final diastolic pressure, DP_(mp) can be computed. As indicated inblock 1885 the final mean profile diastolic pressure DP_(mp) is taken tobe the average of four sequential d(i) values where two of such valueswere computed after the occlusive cuff pressure first became less thanor equal to the D_(n) value.

2.3.2.3.2 Sliding Slope Routine 1037

After the mean profile routine 1033 has been executed, a sliding slopediastolic pressure value DPss is ascertained using sliding slope routine1037 which is shown in flowchart form in FIGS. 20A-B. This routine, likethat of the mean profile routine, is premised on the existence of a widerange of non-linear arterial wall elasticity relationships in the humanpopulation. The object of the sliding slope routine is to produce highlyconsistent and extremely accurate diastolic pressure determinationsthrough measuring independent physiologic phenomena which are moredirectly related to the actual arterial diastolic pressure of anypatient than any method known to the art. This thus contrasts withnon-invasive pressure-sensing diastolic determination methodologiesgenerally known in the art which assume a pre-determined staticrelationship (of pressure/displacement elasticity) and derive diastolicpressure determinations based on linear extrapolation of the mean bloodpressure peak amplitude values.

In particular, the inventive sliding slope method is independent of thepatient's mean blood pressure. In essence, this routine measures theocclusive cuff pressure value at which the declining rate of change ofpressure displacement amplitudes (PWAs) becomes significantly lessnegative, i.e., "flattens-out", as cuff pressure is reduced.Physiologically, this "flattening-out" occurs when the magnitude of theexternally-applied occlusive cuff pressure first becomes less than thatof the intra-arterial diastolic pressure. Thus, after "flattening out"is reached, any further lowering of the resistance (occlusion) to bloodflow becomes less apparent, as indicated by the "bend" in the decliningtrend of amplitude values in the PWA envelope (see FIG. 19B).

To facilitate understanding of sliding slope routine, its operation willfirst be graphically described in conjunction with FIGS. 21A-F, in whichFIGS. 21A-D depict four different illustrative descending sequences ofPWA peaks. Any one of these sequences might occur during occlusive cuffbleed-down, depending on patient condition and movement. FIG. 21Arepresents a sequence of generally descending PWA pulses in which thereis a small amount of peak-to-peak variability. Increasing amounts ofvariability are shown in the sequences depicted in FIGS. 21B-D.

In essence, this routine determines the peak amplitude and correspondingocclusive cuff pressure mid-points between each sequential pair ofdetected PWA peaks. These mid-points are then alternately assigned toone of two overlapping (timewise) sequences--identified as either dotsor triangles in each of FIGS. 21A-F. For example, as shown in FIG. 21A,the dot sequence, labelled SS2, is comprised of mid-points 2, 4, 6, 8and 10; while the triangular point sequence, labelled SS1, is comprisedof mid-points 1, 3, 5, 7 and 9. The adjacent mid-points in each sequenceare connected by line segments (e.g. line segments 1-3, 3-5, 5-7 and 7-9for SS1) followed by a determination of the slope m for each linesegment in each sequence. The slopes for all the segments comprisingeach sequence are then compared with a pre-defined negative thresholdvalue that is used as a criterion for identifying the value of occlusivecuff pressure that corresponds to when the rate of PWA descent(determined by the slope of each line segment) becomes relativelyhorizontal or approaches a less negative value (i.e., begins to"flatten-out"). Specifically, "flattening-out" is defined to haveoccurred in a sequence when two successive segments in that sequencepossess slope values that are less (negative) than, or equal to, thenegative threshold (illustratively and preferably set at a relativelysmall value of approximately -0.25). After the point at which"flattening-out" is said to occur is determined for each overlappingsequence, an intermediate diastolic pressure value, dp_(SS1) anddp_(SS2), is selected for each sequence, SS1 and SS2, respectively. Eachintermediate value is equal to occlusive cuff pressure corresponding tothe respective PWA peaks that immediately precedes the leading mid-point(such as mid-points 5 and 6 in FIG. 21A and those connected torearward-facing arrows in all the FIGS. 21A-F) of preferably thefirst-occurring line segment in each sequence (e.g. segments 5-7 and 6-8in FIG. 21A) that has a slope that is less than the threshold value. Thefinal sliding slope diastolic pressure value, DPss, is then determinedas being equal to dp_(SS1), dp_(SS2), or the average value of both.Preferably and as employed in the embodiment described herein, DPss istaken to be dp_(SS2), the occlusive cuff pressure for the PWAimmediately preceding the second-to-occur leading mid-point (e.g.,mid-point 6 having an occlusive cuff pressure 83 mm(Hg) as shown in FIG.21A), or the minimum of the two intermediate diastolic values.

With abnormal hemodynamic activity, the PWA peak-to-peak variability maybe excessive (such as that shown in FIGS. 21C and 21D) which, in turn,may cause successive line segments to possess a slope value which isalternately less negative than the threshold value and then morenegative. Line segments, which possess such a negative slope, arehereinafter referred to as "negators." To minimize the effect of anynegator(s) on the sliding slope determination of diastolic pressure, thePWA peak that occurs immediately after each leading mid-point of anegator (labelled as "PWX" in FIGS. 21C and 21D) is removed to result inthe sequences shown in FIGS. 21E and 21F which respectively correspondto the original unadjusted sequences depicted in FIGS. 21C and 21D. Inaddition, if a line segment has a slope in excess of a pre-definedpositive threshold, illustratively and approximately (+) 0.25 and occursimmediately prior to any "negator", then it is termed a "reversal", andthe PWA causing the "reversal" (labelled "PWR" in FIG. 21D) is alsoremoved in order to minimize its influence on its associated sequence.The selected PWR is the smaller of the PWA's that immediately proceedand follow the leading mid-point of the "reversal" segment. After allthe necessary PWA's have been removed to eliminate "negators" and"reversals," each mid-point is re-calculated and assigned to one of twosequences, and line segments that join each pair of adjacent mid-pointsfor each sequence are calculated. The final sliding slope diastolicvalue, DPss, is determined in the same manner described above.

With the foregoing in mind, sliding slope routine 1037 will now bedescribed in conjunction with the flowchart shown in FIGS. 20A-B. Uponentry into this routine, execution block 2101 initializes the value ofconstant K₁ to the pre-defined negative threshold value, illustrativelyand preferably -0.25. Thereafter, block 2105 is executed whichcalculates the mid-point co-ordinates (x_(n), y_(n)) for the mid-pointof each adjacent PWA pair, PWA_(n) and PWA_(n+1), using the followingequations:

    x.sub.n =(OCP.sub.n +OCP.sub.n+1)/2

    y.sub.n =(PWA.sub.n +PWA.sub.n+1)/2

and stores the results in RAM. Once this is accomplished, executionblock 2109 successively and alternately assigns these mid-points tosequences SS1 and SS2. The resulting sequences are represented by thefollowing:

    SS1=(X.sub.1,Y.sub.1), (X.sub.3,Y.sub.3) , . . . , (X.sub.n,Y.sub.n)

    SS2=(X.sub.2,Y.sub.2), (X.sub.4,Y.sub.4) , . . . , (X.sub.n+1,Y.sub.n+1)

where SS1 is represented by the "triangular" labelled mid-points inFIGS. 21A-F, and SS2 is represented by the "dotted" labelled mid-pointsalso appearing in these figures.

To facilitate understanding the operation of execution blocks 2113,2117, 2125 and decision block 2121, the operation of these blocks willnow be discussed with specific reference to the sequence of PWAs shownin FIG. 21D. Once the mid-points have been assigned to the appropriatesequences, execution block 2113 computes the slope of the line segmentconnecting each pair of adjacent mid-points in each sequence and storesthe results in RAM memory. In this regard, the following slope valuecomputations illustratively would result from the series of PWAsillustratively shown in FIG. 21D:

    ______________________________________                                        Sequence          Mid-Points                                                  ______________________________________                                        SS1               1, 3, 5, 7, 9, 11, 13                                       SS2               2, 4, 6, 8, 10, 12, 14                                      ______________________________________                                        Sequence SS1 Slopes                                                           Line Segment                                                                            1-3    3-5     5-7  7-9   9-11  11-13                               Slope Values                                                                            -.28   -1.2    +.6  -.24  -.24  -.12                                Sequence SS2 Slopes                                                           Line Segment                                                                            2-4    4-6     6-8  8-10  10-12 12-14                               Slope Values                                                                            -.48   -.92    +.76 -.72  +.08  -.16                                ______________________________________                                    

Thereafter, execution block 2117 compares each slope value against thepre-defined negative value of K₁ (-0.25) and a pre-defined constantpositive threshold (which for purposes of the following discussion willbe set equal to the positive value of K₁, i.e. +0.25) to identify any"negators" and "reversals." In this regard, segment 8-10 of FIG. 21D islabelled as a "negator" and segment 6-8 is labelled as a "reversal." Ifany "negators" and "reversals" are found, block 2117 identifies andstores the previously defined associated PWX and PWR peaks for useduring the diastolic validation routine, which will be discussedshortly. Thereafter, decision block 2121 routes execution via the "Yes"path, to block 2125. This latter block eliminates both the PWX peaksoccurring immediately after the leading mid-points of all "negators",and the PWR peaks occurring immediately before or after the leadingmid-points of all "reversal" line segments. Thereafter, controltransfers to block 2105 which recomputes the mid-points associated withthe remaining PWA's. Blocks 2105 and 2109 thereafter assign each ofthese mid-points to either sequence SS1 or sequence SS2. From there,block 2113 calculates the slope of each line segment connecting anadjacent pair of mid-points in each of these. The following resultsapply to the sequences illustratively shown in FIG. 21F:

    ______________________________________                                        Sequence            Mid-points                                                ______________________________________                                        SS1                 1,3,5,7,9,11                                              SS2                 2,4,6,8,10,12                                             ______________________________________                                        Sequence SS1 Slopes                                                           Line Segment                                                                             1-3      3-5    5-7    7-9  9-11                                   Slope Values                                                                             -.28     -.56   -.27   -.1  -.12                                   Sequence SS2 Slopes                                                           Line Segment                                                                             2-4      4-6    6-8    8-10 10-12                                  Slope Values                                                                             -.48     -.19   -.4    +.08 -.16                                   ______________________________________                                    

In the event of an extremely sharp or flat descending PWA envelope, thenthe value of the negative threshold constant, K₁, is modified by block2117. For example, if the envelope is characterized by a relatively lownumber of PWAs and a pronounced peak value, then the value of constantK₁ may be preferably set to approximately -0.5. Alternatively, if theenvelope is relatively flat and its latter stage descent is verygradual, then the value of constant K₁ may preferably be set to a muchlower value, such as approximately -0.1. Selection of the appropriatevalue of this constant is accomplished by computing the overall rate ofchange in the envelope between the peak envelope amplitude and theapproximate diastolic amplitude value. Alternatively, this computationmay be combined with the determination of the average rate of change ofPWA amplitudes detected prior to the maximum PWA value being reached inthe envelope pressure determination. Either of these alternativelycomputed rate of change factors are then illustratively used to addressan appropriate look-up table in order to access one or severalpredetermined values of constant K₁ . Alternatively, the determinationof K₁ may actually be accomplished by computing the quotient of thevalue of PWA_(peak) divided by the total number of PWAs detected (duringthe occlusive cuff measurement routine) that occur prior to the one PWAselected as being the final diastolic pressure.

If, after execution of block 2117, decision block 2121 determines thatno "negators" or "reversals" remain, then execution block 2129determines an intermediate diastolic value, dp_(SS1) and dp_(SS2), foreach series SS1 and SS2, respectively. Specifically, block 2129 examinesthe slopes for each sequence to find two adjacent slope values that aresmaller than the current positive and negative threshold values (whichfor purposes of the example shown in FIG. 21F is ±0.25) such as segmentpairs 7-9 and 9-11, as well as 8-10 and 10-12. Each intermediatediastolic value is then set equal to the occlusive cuff pressure of thePWA occurring immediately prior to the leading mid-point of the firstline segment in each sequence that has a slope which is smaller than thethreshold value (such as segments 5-7 and 6-8 in FIG. 21F correspondingto occulsive cuff pressures 83 and 78, respectively). Lastly, block 2133selects the final sliding slope diastolic pressure value, DP_(SS), asbeing the minimum of the two intermediate values, which illustrativelyfor this example (FIG. 21F) is 78 mm.

At this phase in the occlusive cuff measurement process, i.e. after bothdiastolic values (DP_(mp) and DP_(ss)) have been determined by meanprofile and sliding slope routines 1033 and 1037, respectively,execution then passes to diastolic validation routine 1040.

2.3.2.4 Diastolic Validation Routine 1040

Diastolic validation routine 1040 is shown in flowchart form in FIG. 22.This routine compares the results of the diastolic mean profile andsliding slope routines to select the one that best produces a validmeasure of diastolic pressure. Specifically, the selection entailsdetermining which of the two independent diastolic determinationroutines performed most effectively in view of the actual hemodynamicdata encountered during the diastolic measurement phase of the occlusivecuff process. This selection is facilitated since each of the tworoutines produces an accompanying set of hemodynamic variability datathat indicates the relative accuracy of each of the two intermediatediastolic measurement values, Dp_(mp) and DP_(ss). When these two valuesdiffer from each other by any significant amount, i.e., 5%, the"selection" is performed based on accessing a pre-determined look-uptable that determines which routine is likely to produce the mostaccurate measurement value. In addition, the value produced by eachroutine is "validated" through criteria--as previouslydiscussed--resident within each routine which selects a result which isleast influenced by hemodynamic variability and also establishes limitson maximum acceptable variability for the selected result. If thevariability data of both routines exceeds the limits, a final diastolicpressure measurement value DP does not occur, and the entire occlusivecuff measurement process is repeated.

Specifically, upon entry into diastolic validation routine 1040,decision block 2301 tests both diastolic pressure values, DPmp and DPss,to see if they are within a pre-defined percentage, illustratively±21/2%, of each other. If they are, the final diastolic pressure, DP, ismerely taken, via block 2305, as the average of the mean pressure andsliding slope diastolic values. Once this final pressure is determinedand appropriately displayed and transmitted, via bi-directional port 232(see FIG. 1B), execution exits from block 2305 to the previouslydescribed elasticity moduli table determination routine 640.

Alternatively, if the difference between these diastolic values isgreater than illustratively ±21/2%, then execution proceeds, via the"No" path, from decision block 2301, to block 2309. Such a largemeasurement differential is generally due to significant variabilityamong detected PWA peaks and, to confirm this, block 2309 removes fromthe final mean profile average computation, the individual PWA peakvalues, if any, attributable to "reversals" and "negators" designated inthe sliding slope routine and then re-computes the diastolic pressurevalue DP_(mp) using only the remaining PWA peak values. If, decisionblock 2313 determines that the re-computed mean profile value DP_(mp) isthen within ±5% of the sliding slope DPss value, then executionproceeds, via the "Yes" path from block 2313, to block 2305.

If, however the remaining difference between these diastolic values,DP_(mp) and DP_(ss), is still greater than illustratively 5%, control isrouted from decision block 2313 to decision block 2317. If the amount ofvariability inherent in the data used in both the sliding slope and meanprofile methods is excessive, then neither DPss or DPmp pressuremeasurements can be relied upon for an accurate final diastolicmeasurement. Specifically, block 2317 tests for the existence of anexcessive level of variability, and if this is found, the currentocclusive cuff measurement process is first terminated through executionof block 2321 and second another occlusive cuff measurement process isinitiated by transferring control to cuff inflation routine 770.Specifically, if one "negator" or more than one "negator" or "reversal"was identified during the sliding slope routine and the differentialrange of individual PWA diastolic values, d(i-3) through d(i),determined in the mean profile routine exceeds 16%, then decision block2317 transfers control to execution block 2321 which terminates thepresent occlusive cuff measurement process.

Alternatively, if the variability is not excessive, then control passes,via the "no" path from decision block 2317, to execution block 2325which uses a selection matrix to select either DPmp or DPss as the finaldiastolic pressure, DP. Specifically, the selection matrix thatspecifies the particular value based on a computed percentagedifferential of individual PWA diastolic values d(i) and the previouslydetermined total number of "negators" and "reversals." An illustrativeselection matrix is provided below; however the particular selectioncriteria used in practice may based upon empirical study vary from thatindicated therein.

    ______________________________________                                                     Range Variation of Individual                                                 Mean Profile Diastolic Values                                                 Used for DPmp Computations                                       Sliding Slope                                                                              Percentage Differential                                          Variability  0 to ±6%                                                                             ±6 to 12%                                                                            ±12% or more                              ______________________________________                                        No negators  SS        SS        SS                                           One negator  MP        Average   SS                                           Two or more negators                                                                       MP        MP        MP                                           or reversals                                                                  ______________________________________                                         where SS signifies sliding slope method-use DPss value; MP signifies mean     pressure method-use DPmp value; and "Average" signifies taking the averag     of DPss and DPmp.                                                        

It is quite apparent that the use of both separate occlusive andwaveform sensing cuffs enables the system to be connected to severallimb positions of the patient; preferably the two cuffs are positionedon the patient's opposite upper arms or thighs. However, when medicaltreatment dictates that the cuffs be positioned on the same limb, theconstant pressure waveform sensing cuff is preferably located distal(e.g. at the wrist or ankle) to the position of the occlusive cuff (e.g.upper arm or thigh). In these specialized situations, constant pressurecalibration sampling using the waveform sensing cuff cannot occur untilafter the systolic and diastolic calibration values are determined viaocclusive cuff. Thus, in these situations, computer 200 detects theabsence of any pulses detected through the waveform sening cuff and, inresponse thereto, extends the length of "calibration" phase until allresidual applied occlusive cuff pressure has been eliminated in order topermit additional pressure displacement waveform sampling for thedetermination of base level, peak, trough, and reference pressurevalues. Consequently, during any such "calibration" phase, which canextend to a total duration of about 40 seconds, continuous pressuremonitoring based on the look-up table data (from the prior calibrationphase) is interrupted in lieu of being performed essentiallysimultaneously with, the current "calibration" phase as in the preferredembodiment described above.

During any "calibration" phase, using opposite limb connections, eachheart-beat-generated pressure waveform is simultaneously detected as aseries of pressure displacement waveform values as part of both theocclusive cuff pressure perturbations and perturbations to the constantreference pressure signal produced by the waveform sensing cuff.Simultaneous, or near simultaneous sampling (detection timingdifferences result from different arterial pathway distances to each ofthe cuffs and waveform propogation rates therethrough) of eachsequentially occurring waveform at different artery-limb locations andapplied pressure values enables highly accurate definition ofhemodynamic activity during the occlusive cuff calibration measurementroutines.

Computer 200 also determines if the two cuffs are affixed to differentlimbs, inasmuch as this is the preferred interconnection scheme forcontinuous monitoring. This scheme is identified as existing if pressuredisplacement waveforms detected through the waveform sensor cuff are notattenuated during inflation of the occlusive cuff to suprasystolicpressure during execution of any "calibration" phase. Once opposite limbinterconnection has been identified, certain simplified measurementprocesses and supplemental processes, as will now be described, areimplemented during the "calibration" and "continuous monitoring" phases.First, execution block 1271 computations of API values in Pulse WindowInterrogation (PWI) routine 1250 (which is executed in conjunction withsystolic routine 1020) is simplified by the fact that heart-ratewaveform peak-to-peak intervals are determined based on low pressurewaveform sensing cuff sampling instead of being being taken fromocclusive cuff sample data. Thus, blocks 1261-1265 of the PWI routine(see FIG. 13A) are not used during calibration with opposite limbsensing, and occlusive cuff absent pulse windows (APW) areinstantaneously identified, without the use of TAPW designations andredesignations, during systolic routine 1020. Second, opposite limbsensing provides for effective identification of the occurrence of anyartifacts (e.g., aberrant limb movement data that can obfuscate validpressure displacement waveform sampling data) so that false data can beidentified and rejected in order to prevent erroneous calibrationmeasurement values. Specifically, a comparison of the two opposite limbsampling sequences of PWA values readily enables the identification ofany artifact "pulse" occurring in either sequence. If a disproportionatepeak amplitude value, with respect to one or more prior and subsequentamplitude values, is measured in a waveform in one of the two sequences,disproportionate peak amplitude value must exist with respect to thecorresponding waveform in the other sequence. If a disproportionatevalue exists in the PWA sequence produced through one cuff but not inthat produced by the other cuff, then this disproportionate value isidentified as an artifact instead of as a valid pressure displacementwaveform and is thus not used in the measurement process. While thiscomparative process can be used to test either sampling sequence forartifacts, this process is particularly germane to the occlusive cuffsampling data where artifact amplitudes can be similar in relativemagnitude to those of pressure displacement waveforms occurring duringexecution of occlusive cuff measurements routine 630.

While the preferred embodiment of the non-invasive blood pressuremeasurement system previously described herein involves the use of twoseparate cuffs--one for occlusive cuff calibration measurement and theother for pressure displacement waveform monitoring at a constant lowpressure, it is readily apparent that a single occlusive cuff and asingle channel of analog electronic components might alternatively beemployed. The methods of the preferred embodiment, as described abovewith respect to two cuffs interconnected to the same limb, wouldgenerally be used even if single, occlusive blood pressure cuff were tobe used instead. Specifically, the system would generally operate asdescribed above, although continuous monitoring would be interruptedduring the "calibration" phase. Furthermore, at the completion ofocclusive cuff measurement routine 630, the occlusive cuff pressurewould be abruptly deflated to approximately 40 mm(Hg). Thereafter,sampling for the "continuous monitoring" phase, would proceed using theocclusive cuff channel in lieu of a separate waveform sensor cuffchannel.

Of course, it is readily apparent for those skilled in the art thatwhile the invention has been described in terms of a system formeasuring human blood pressure, the invention can be easily extended toa system for measuring the pressure of any pulsatile flowing fluid. Thebasic requirement for any such system is that the fluid must flowthrough an elastic tube in which the radial distension (movement) of thewall of the tube varies as a pre-defined function of the fluidicpressure therein. This distension/pressure function can be either linearor non-linear. Means such as, but not limited to, electrically-operatedvalves and the like, can be used to restrict or stop the pulsatile fluidflow in order to establish a plurality of pre-defined walldistension/fluid pressure boundary conditions. The particular meanschosen may be dependent upon various physical properties of the actualfluid being measured, such as but not limited to its corrosivity, andvarious other physical constraints, such as but not limited to whether avessel of appropriate elastic properties can be easily inserted anywheredownstream of the point at which the flow restricting device isinstalled. During execution of the "calibration" phase, the measureddistension of the wall of the tube occurring at each of the boundaryconditions is used to determine the values of all the necessarycoefficients appearing in the pre-defined radial walldistension/pressure function. Thereafter, the system "continuouslymonitors" the pressure based upon any subsequently occurring walldistensions. Re-calibration is initiated at discrete intervals of timeto insure accurate pressure readings. The durations of these intervalsmight be long (e.g., weeks or months) or short, depending on thephysical characteristics of the system, and might adaptively changebased upon the amount of variation in the value of one or more of thesecoefficients occurring between any past calibration interval, such asthe most recent one, to another calibration interval, such as thepresent one. As the amount of this variation increased, the durationbetween successive re-calibrations correspondingly decreases. Likewise,if little variation occurred, then this duration correspondinglyincreases.

Although a specific illustrative embodiment has been shown and describedherein, this merely illustrates the principles of the present invention.Many varied arrangements embodying these principles may be devised bythose skilled in the art without departing from the spirit and scope ofthe invention.

I claim:
 1. A method tor use in determining arterial blood pressure in asubject comprising the steps of:undertaking a calibration phasecomprised of the steps of determining blood pressure and arterial walldisplacement values of said subject occurring in response tocorresponding initial conditions of blood flow, and ascertaining, inresponse to said determined values, the values of a plurality ofcoefficients, each of which is associated with a corresponding term in apre-defined relationship that characterizes arterial blood pressure as afunction of arterial wall displacement, undertaking a continuousmonitoring phase comprised of the steps of measuring subsequentlyoccurring actual arterial wall displacement values, generating acorresponding blood pressure value in response to said relationship andto at least one of each of said actual arterial displacement values, andrepeating said calibration phase at the occurrence of any one of aplurality of pre-defined events or at pre-defined times.
 2. The methodof claim 1 wherein said continuous monitoring phase undertaking step isfurther comprised of the step or varying said times in response todifferences between the most recent value and a corresponding priorvalue of at least one of said coefficients.
 3. The method of claim 2wherein said generating step is further comprised of the step ofproducing various measurement parameters based upon said generated bloodpressure values.
 4. The method of claim 3 wherein said repeating step iscomprised of the steps of:checking various ones of said measurementparameters against corresponding limit values, and repeating saidcalibration phase whenever at least one of said measurement parametersexceeds its corresponding limit value.
 5. The method of claim 1 whereinsaid determining step is comprised of the steps of:affixing at least onearterial occluding device to at least one limb of a subject,controllably operating said occluding device to non-invasively occludean artery within said limb and thereby establish an initial condition ofarterial blood flow, sensing perturbations, in the arterial blood flowthrough said occluding device, as said device reduces its occlusion at acontrolled rate so as to establish other initial conditions of arterialblood flow, and determining, in response to the value of saidperturbations, values of arterial blood pressure and arterial walldisplacement occurring at each of said initial conditions of arterialblood flow.
 6. The method of claim 5 in which said operating stepfurther includes the step of measuring said perturbations through saidoccluding device and controllably increasing the occlusion produced bysaid device to a value in excess of that required to eliminate saidperturbations, whereby an initial condition of supra-systolic occlusionis achieved.
 7. The method of claim 6 in which said measuring stepincludes the step of inflating a pneumatic cuff attached around aselected limb of the subject and sensing pulsatile perturbationsoccurring in the air contained in the cuff and attributable to pulsatilearterial blood flow.
 8. The method of claim 7 in which said inflatingstep further includes the steps of:attaching a relatively high pressureocclusive pneumatic cuff and a low pressure waveform sensing cuff aroundat least one limb of the subject, controllably inflating the occlusivecuff first to a supra-systolic occlusive pressure and then deflating theocclusive cuff to a sub-diastolic occlusive pressure in order to producesaid initial conditions of arterial blood flow, inflating said lowpressure waveform sensing cuff simultaneously with said occlusive cuffand thereafter maintaining air pressure at a substantially constant lowpressure during deflation of said occlusive cuff, and measuring therelative displacement of the arterial wall attributable to the arterialblood flow occurring for each of said initial conditions as a functionof the simultaneously occurring pulsatile variation in the pressure ofsaid waveform sensing cuff.
 9. The method of claim 8 wherein theattaching step further includes the steps of securing the occlusive cuffaround a selected limb of the subject and securing the waveform sensingcuff on the same limb but at a location distally situated from saidocculsive cuff.
 10. The method of claim 8 wherein the attaching stepfurther includes the step of securing the occlusive and waveform sensingcuffs to different limbs of the subject.
 11. The method of claim 10wherein the securing step includes the step of positioning the occlusiveand waveform sensing cuffs on opposite limbs of the subject.
 12. Themethod of claim 1 wherein the ascertaining step further includes thestep of substituting each of a pre-selected plurality of arterial walldisplacement values into said pre-defined relationship in order tofabricate a table of arterial blood pressure values corresponding tosaid pre-selected plurality of displacement values.
 13. The method ofclaim 12 wherein the generating step includes the step of using at leastone of said actual arterial displacement values to access the table inorder to determine a generated blood pressure value correspondingthereto.
 14. The method of claim 13 wherein the generating step isfurther comprised of fabricating a sequence of present and previouslygenerated blood pressure values for display on an historical basis. 15.The method of claim 14 wherein the generating step is further comprisedof fabricating respective sequences of present and prior values for eachof a plurality of measurement parameters, wherein said parameters aredetermined in response to said generated blood pressure values.
 16. Themethod of claim 15 wherein the generating step is further comprised ofproviding a suitable notification whenever any value of any of saidsequences exceeds a pre-defined limit value.
 17. The method of claim 16wherein the fabricating step includes the step of producing systolic anddiastolic arterial blood pressure values.
 18. The method of claim 1wherein said determining step further includes the step of producing asystolic blood pressure value, and generating at least first and seconddiastolic blood pressure measures and selecting either one of saidmeasures as a final diastolic pressure value in response to hemodynamicvariability detected during said calibration phase.
 19. The method ofclaim 18 wherein said systolic value producing step includes the stepsof:controllably deflating an occlusive cuff secured around a limb of thesubject, detecting a pre-determined number of pressure waveform peaksand simultaneously occurring corresponding occlusive cuff pressuresoccurring during occlusive cuff deflation, determining a measure of thevariability of these detected peaks, defining co-ordinates of a firstpoint in terms of an average of the detected peaks and an average of thecorresponding occlusive cuff pressures, successively maintaining thepressure of said occlusive cuff at a substantially constant value for acorresponding pre-selected time interval and detecting additionalpressure waveform peaks and determining a second measure of thevariability associated therewith during said corresponding timeinterval, defining co-ordinates of a second point in terms of an averageof said additional peaks and said constant pressure value, modifying thevalues of the co-ordinates of said first and/or second points, inresponse to said first and/or second variability measures, ascertainingan intermediate value of systolic pressure in terms of the co-ordinatesof a point of intersection between a line defined by said first andsecond points and a line representing a pre-determined constant pressurevalue, and modifying said intermediate systolic pressure value inresponse to said first and/or second variability measures so as toobtain a final systolic pressure value.
 20. The invention in claim 19 inwhich said deflating step further includes the step of deflating theocclusive cuff at a pre-defined controlled linear rate.
 21. Theinvention in claim 19 in which the peak detecting step includes the stepof sampling pneumatic pressure of said occlusive cuff during each of apre-defined number of sequentially occurring sampling windows, each ofsaid windows being a pre-determined duration, to detect either apressure waveform peak or an absent pulse occurring during any of saidwindows.
 22. The invention in claim 21 in which the sampling stepfurther includes the step of varying the duration of said samplingwindows in response to either the actual heart-rate of the subjectand/or previously occurring absent pulse windows.
 23. The invention inclaim 19 in which said maintaining step includes the step of selectingthe duration of said pre-selected time interval based upon the number ofpressure peaks and absent pulse windows and the order in which saidpeaks and absent pulse windows occur during this interval.
 24. Theinvention in claim 23 in which said maintaining step further includesthe step of determining the value of said variability measure in termsof the number of absent pulse windows detected during a pre-selectedsequence of sampling windows.
 25. The invention in claim 19 in whichsaid intermediate systolic value ascertaining step includes the step ofdetermining the x co-ordinate value of said point of intersection andsetting said intermediate systolic value equal to the value of the xco-ordinate.
 26. The invention in claim 18 in which said first diastolicmeasure generating step includes the steps of:determining a group, of apre-selected number of sequentially occurring individual pressurewaveform values, from all the pressure waveforms occurring duringdeflation of an occlusive cuff, wherein said group possesses maximumaverage amplitude, selecting, in accordance with pre-selected criteria,at least one individual pressure waveform from the group and settingmean pressure of the subject equal to the occlusive cuff pressurecorresponding to the selected individual pressure waveform, determiningthe systolic pressure of the subject, and ascertaining the first measureof diastolic pressure in accordance with the formula: ##EQU2## for atleast a chosen one of all of said pressure waveforms in which D is thefirst measure of diastolic pressure, A is the uncalibrated peakamplitude of said chosen pressure waveform, Y is the mean value(area/duration) of said chosen pressure waveform, and S and M are thesystolic and mean pressure values respectively, associated with saidsubject.
 27. The invention in claim 26 in which said selecting step iscomprised of the steps of determining a second group of a preselectednumber of sequentially occurring pressure waveforms from all of saidwaveforms occurring subsequent to said selected individual pressurewaveform.
 28. The invention in claim 27 in which the selecting stepincludes the step of ascertaining the mean pressure as beingsubsequently equal to the occlusive cuff pressure occurring at the timeof the peak of said selected individual pressure waveform.
 29. Theinvention in claim 28 in which the first measure ascertaining stepfurther includes the step of determining, in accordance with saidformula, a diastolic pressure estimate for each pressure waveform insaid second group and averaging all the estimates to produce said firstmeasure of diastolic pressure.
 30. The invention in claim 26 in whichsaid individual pressure waveform selecting step is comprised of thesteps of:determining whether said selected individual waveform wascaused by an artifact by comparing the peak amplitude of said selectedindividual waveform against a pre-determined limit, and rejecting theselected individual waveform in the event the limit is exceeded andselecting another waveform until such limit is no longer exceeded. 31.The invention in claim 18 in which said second diastolic measuregenerating step includes the steps of:a. establishing, in response to asequence of occlusive pressure waveform peaks and correspondingocclusive cuff pressures occurring during deflation of the occlusivecuff, a sequence of mid-point co-ordinates, wherein one co-ordinate ofeach midpoint is an average of the peak amplitudes of two successivepressure waveforms and the other co-ordinate of each mid-point is anaverage of the occlusive cuff pressures corresponding to each of saidtwo peaks, b. grouping every mid-point into an alternate one of at leasttwo series, c. determining the value of slope of each of a plurality ofline segments, wherein each segment joins a pair of adjacent midpointsin one of said sequences, d. testing each of said slope values againstpre-defined limits to determine whether any of said mid-points isattributable to a negator or a reversal, e. removing any pressurewaveform peak and its corresponding occlusive cuff pressure valueattributable to a negator or a reversal from the sequence and repeatingsteps (a), (b), (c) and (d) until substantially all pressure waveformpeaks attributable to either negators or reversals have been removed, f.comparing the slope of each segment in each series against a pre-definedthreshold and, in response thereto, choosing an appropriate one of thesegments comprising each series, g. choosing an appropriate pressurewaveform peak amplitude value that precedes the leading midpointassociated with the chosen segment in each series, and h. selecting oneof the resulting chosen pressure waveform peak amplitude values as thesecond diastolic measure.
 32. The invention in claim 31 wherein saidselecting step includes the step of picking that one of the chosenwaveform peak amplitude values which has the minimum peak amplitude asthe second diastolic measure.
 33. The invention in claim 18 wherein saidselecting step includes the step of picking said first, said second, oran average of said first and second diastolic pressure measures for saidfinal diastolic pressure value in response to a numerical differencebetween the values of said first and second measures and/or the numberof negators and reversals determined during said second diastolicmeasuring step.
 34. Apparatus for determining arterial blood pressure ina subject comprising:means for undertaking a calibration phasecomprising means for determining the blood pressure values occurring inresponse to corresponding initial conditions of blood flow, and meansfor ascertaining, in response to said determined blood pressure values,the values of a plurality of coefficients, each of which is associatedwith a corresponding term in a pre-defined relationship thatcharacterizes arterial blood pressure as a function of arterial walldisplacement, means for undertaking a monitoring phase comprising meansfor measuring subsequently occurring acutal arterial wall displacementvalues, means for generating a corresponding blood pressure value inresponse to said relationship and to at least one of each of said actualarterial displacement values, and means for repeating said calibrationphase at the occurrence of any one of a plurality of pre-defined eventsor at pre-defined times.
 35. The apparatus of claim 34 wherein saidmonitoring phase undertaking means is further comprised of means forvarying said times in response to differences between the most recentvalue and a corresponding prior value of at least one of saidcoefficients.
 36. The apparatus of claim 35 wherein said generatingmeans is further comprised of means for producing various measurementparameters based upon said generated blood pressure values.
 37. Theapparatus of claim 36 wherein said repeating means is comprised of:meansfor checking various ones of said measurement parameters againstcorresponding limit values, and means for repeating said calibrationphase whenever at least one of said measurement parameters exceeds itscorresponding limit value.
 38. The apparatus of claim 37 wherein saiddetermining means is comprised of:means for occluding an artery situatedin one limb of a subject, means for controllably operating saidoccluding means to non-invasively occlude said artery within said limband thereby establish an initial condition of arterial blood flow, meansfor sensing perturbations, in the arterial blood flow through saidoccluding means, as said occluding means reduces its occlusion at acontrolled rate so as to establish other initial conditions of arterialblood flow, and means for determining, in response to the value of saidperturbations, values of arterial blood pressure and arterial walldisplacement occurring at each of said initial conditions of arterialblood flow.
 39. The apparatus of claim 38 in which said operating meansis comprised of: means for measuring said perturbations through saidoccluding means and controllably increasing the occlusion produced bysaid occluding means to a value in excess of that required to eliminatesaid perturbations, whereby an initial condition of supra-systolicocclusion is achieved.
 40. The apparatus of claim 39 in which saidmeasuring means includes means for inflating a pneumatic cuff attachedaround a selected limb of the subject and sensing pulsatileperturbations occurring in the air contained in the cuff andattributable to pulsatile arterial blood flow.
 41. The apparatus ofclaim 40 in which said inflating means is comprised of:a relatively highpressure occlusive pneumatic cuff and a low pressure waveform sensingcuff, each of which is attached around at least one limb of the subject,means for controllably inflating the occlusive cuff first to asupra-systolic occlusive pressure and then deflating the occlusive cuffto a sub-diastolic occlusive pressure in order to produce said initialconditions of arterial blood flow, means for inflating said low pressurewaveform sensing cuff simultaneously with said occlusive cuff andthereafter maintaining air pressure at a substantially constant lowpressure during deflation of said occlusive cuff, and means formeasuring the relative displacement of the arterial wall attributable tothe arterial blood flow occurring for each of said initial conditions asa function of the simultaneously occurring pulsatile variation in thepressure of said waveform sensing cuff.
 42. The apparatus of claim 41wherein the occlusive cuff is secured around a selected limb of thesubject and the waveform sensing cuff is secured around the same limbbut at a location distally situated from said occlusive cuff.
 43. Theapparatus of claim 41 wherein the occlusive and waveform sensing cuffsare secured around different limbs of the subject.
 44. The apparatus ofclaim 43 wherein the occlusive and waveform sensing cuffs are securedaround opposite limbs of the subject.
 45. The apparatus of claim 34wherein the ascertaining means is comprised of means for substitutingeach of a pre-selected plurality of arterial wall displacement valuesinto said pre-defined relationship in order to fabricate a table ofarterial blood pressure values corresponding to said pre-selectedplurality of displacement values.
 46. The apparatus of claim 45 whereinthe generating means comprises means for accessing the table, using atleast one of said actual arterial displacement values, in order todetermine a generated blood pressure value corresponding to saidarterial displacement value.
 47. The apparatus of claim 46 wherein thegenerating means is further comprised of means for fabricating asequence of present and previously generated blood pressure values fordisplay on an historical basis.
 48. The apparatus of claim 47 whereinthe generating means is further comprised of means for fabricatingrespective sequences of present and prior values for each of a pluralityof measurement parameters, wherein said parameters are determined inresponse to said generated blood pressure values.
 49. The apparatus ofclaim 48 wherein the generating means is further comprised of means forproviding a suitable notification whenever any value of any of saidsequences exceeds a pre-defined limit value.
 50. The apparatus of claim48 wherein the fabricating means is comprised of means for producingsystolic and diastolic arterial blood pressure values.
 51. A method foruse in determining arterial blood pressure in a subject, comprising thesteps of:undertaking a calibration phase comprised of the steps ofdetermining blood pressure values and values of a physiologic parameterof said subject related to blood pressure both values occurring inresponse to corresponding initial conditions of blood flow, andascertaining, in response to said determined values, the values of aplurality of coefficients, each of which is associated with acorresponding term in a pre-defined relationship that characterizesarterial blood pressure as a function of said physiologic parameter; andundertaking a continuous monitoring phase comprised of the steps ofmeasuring subsequently occurring actual values of said physiologicparameter, generating a corresponding blood pressure value in responseto said relationship and to at least one of each of said actualphysiologic parameter values, and repeating said calibration phase atthe occurrence of any one of a plurality of pre-defined events or atpre-defined times.
 52. The method of claim 51 wherein the determiningand measuring steps include the step of detecting the physiologicparameter through non-invatsive means or through perivascular invasivemeans, and wherein the physiologic parameter is proportional to arterialwall displacement, arterial blood flow, arterial blood volume orarterial blood velocity.
 53. The method of claim 52 wherein thedetecting step further includes the step of sensing said physiologicparameter through non-invasive strain gage plethysmography or electricalimpedance plethysmography.
 54. The method of claim 52 wherein saidcontinuous monitoring phase further includes the step of varying saidtimes in response to differences between the most recent value and acorresponding prior value of at least one of said coefficients.
 55. Themethod of claim 54 wherein said generating step includes the step ofproducing various measurement parameters based upon said generated bloodpressure values, and said repeating step includes the steps of: checkingvarious ones of said measurement parameters against correponding limitvalues, and repeating said calibration phase whenever at least one ofsaid measurement parameters exceeds its corresponding limit value. 56.The method of claim 52 wherein the ascertaining step further includesthe step of substituting each of a pre-selected plurality of saidphysiologic parameter values into said pre-defined function in order tofabricate a table or arterial blood pressure values corresponding tosaid pre-selected plurality of physiologic parameter values, and saidgenerating step further includes the step of using at least one of saidactual physiologic parameter values to access the table in order todetermine a generated blood pressure value corresponding thereto. 57.The method of claim 56 wherein the generating step further includes thestep of fabricating a sequence of present and previously generated bloodpressure values and, in response thereto, producing systolic anddiastolic arterial blood pressure values.